rs17629216

Variant names:

• chr5-141152828-G-A
• rs17629216
• NM_018939.4:c.*186G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-141152828-G-A
• chr5-141152828-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018939.4(PCDHB6):​c.*186G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 458,712 control chromosomes in the GnomAD database, including 599 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.044 (179 hom., cov: 32)
  • Exomes 𝑓: 0.049 (420 hom.)
• Consequence: PCDHB6 NM_018939.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 9 publications found

Genes affected

PCDHB6 (HGNC:8691): (protocadherin beta 6) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. Unlike the alpha and gamma clusters, the transcripts from these genes do not share common 3' exons. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell neural connections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

PCDHB@ (HGNC:8679):

ENSG00000280029 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018939.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHB6	NM_018939.4	MANE Select	c.*186G>A		3_prime_UTR	Exon 1 of 1	NP_061762.2
	PCDHB6	NM_001303145.2		c.*186G>A		3_prime_UTR	Exon 2 of 2	NP_001290074.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHB6	ENST00000231136.4	TSL:6 MANE Select	c.*186G>A		3_prime_UTR	Exon 1 of 1	ENSP00000231136.1
	PCDHB6	ENST00000622991.1	TSL:2	c.*186G>A		3_prime_UTR	Exon 2 of 2	ENSP00000485034.1
	ENSG00000280029	ENST00000624192.1	TSL:5	n.73-15645C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6733 AN: 151466 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0173

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0414

GnomAD4 exome AF: 0.0495 AC: 15193 AN: 307130 Hom.: 420 Cov.: 5 AF XY: 0.0501 AC XY: 7750 AN XY: 154614

African (AFR) AF: 0.0270 AC: 216 AN: 8000

American (AMR) AF: 0.0322 AC: 294 AN: 9120

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 485 AN: 9206

East Asian (EAS) AF: 0.0000905 AC: 2 AN: 22100

South Asian (SAS) AF: 0.0155 AC: 80 AN: 5170

European-Finnish (FIN) AF: 0.0567 AC: 1924 AN: 33918

Middle Eastern (MID) AF: 0.0527 AC: 71 AN: 1346

European-Non Finnish (NFE) AF: 0.0566 AC: 11357 AN: 200510

Other (OTH) AF: 0.0430 AC: 764 AN: 17760

GnomAD4 genome AF: 0.0444 AC: 6734 AN: 151582 Hom.: 179 Cov.: 32 AF XY: 0.0432 AC XY: 3200 AN XY: 74012

African (AFR) AF: 0.0283 AC: 1168 AN: 41222

American (AMR) AF: 0.0368 AC: 560 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 193 AN: 3468

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5162

South Asian (SAS) AF: 0.0179 AC: 86 AN: 4806

European-Finnish (FIN) AF: 0.0573 AC: 599 AN: 10458

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0583 AC: 3958 AN: 67940

Other (OTH) AF: 0.0410 AC: 86 AN: 2100

Alfa AF: 0.0488 Hom.: 383

Bravo AF: 0.0415

Asia WGS AF: 0.00924 AC: 33 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.50
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs17629216; hg19: chr5-140532409;