rs148748054

Variant names:

• chr5-141351482-C-A
• rs148748054
• NM_018922.3:c.1222C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-141351482-C-A
• chr5-141351482-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_018922.3(PCDHGB1):​c.1222C>A​(p.Arg408Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,613,848 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0065 (39 hom.)
• Consequence: PCDHGB1 NM_018922.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.127
• Publications: 0 publications found

Genes affected

PCDHGB1 (HGNC:8708): (protocadherin gamma subfamily B, 1) This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

PCDHGA2 (HGNC:8700): (protocadherin gamma subfamily A, 2) This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

PCDHGA3 (HGNC:8701): (protocadherin gamma subfamily A, 3) This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

PCDHGA1 (HGNC:8696): (protocadherin gamma subfamily A, 1) This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

PCDHG@ (HGNC:8695):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 5-141351482-C-A is Benign according to our data. Variant chr5-141351482-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2655842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.127 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHGB1	NM_018922.3	MANE Select	c.1222C>A	p.Arg408Arg	synonymous	Exon 1 of 4	NP_061745.1	Q9Y5G3-1
	PCDHGA2	NM_018915.4	MANE Select	c.2424+10087C>A		intron	N/A	NP_061738.1	Q9Y5H1-1
	PCDHGA3	NM_018916.4	MANE Select	c.2424+5025C>A		intron	N/A	NP_061739.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHGB1	ENST00000523390.2	TSL:1 MANE Select	c.1222C>A	p.Arg408Arg	synonymous	Exon 1 of 4	ENSP00000429273.1	Q9Y5G3-1
	PCDHGA3	ENST00000253812.8	TSL:1 MANE Select	c.2424+5025C>A		intron	N/A	ENSP00000253812.7	Q9Y5H0-1
	PCDHGA2	ENST00000394576.3	TSL:1 MANE Select	c.2424+10087C>A		intron	N/A	ENSP00000378077.2	Q9Y5H1-1

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 840 AN: 152202 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00477

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00648

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00653 AC: 1624 AN: 248792 AF XY: 0.00641

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.0259

Gnomad NFE exome AF: 0.00769

Gnomad OTH exome AF: 0.00711

GnomAD4 exome AF: 0.00655 AC: 9569 AN: 1461528 Hom.: 39 Cov.: 33 AF XY: 0.00636 AC XY: 4627 AN XY: 727034

African (AFR) AF: 0.00105 AC: 35 AN: 33478

American (AMR) AF: 0.00269 AC: 120 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00134 AC: 116 AN: 86250

European-Finnish (FIN) AF: 0.0260 AC: 1387 AN: 53366

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00683 AC: 7599 AN: 1111786

Other (OTH) AF: 0.00502 AC: 303 AN: 60368

GnomAD4 genome AF: 0.00552 AC: 841 AN: 152320 Hom.: 6 Cov.: 33 AF XY: 0.00615 AC XY: 458 AN XY: 74470

African (AFR) AF: 0.00118 AC: 49 AN: 41572

American (AMR) AF: 0.00483 AC: 74 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4828

European-Finnish (FIN) AF: 0.0240 AC: 254 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00648 AC: 441 AN: 68030

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00427 Hom.: 1

Bravo AF: 0.00384

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00529

EpiControl AF: 0.00535

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	8.1
DANN	Benign	0.81
PhyloP100		-0.13
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs148748054; hg19: chr5-140731049;