5-141864081-A-G

Variant names:

• chr5-141864081-A-G
• rs3797054
• NM_032420.5:c.2250T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032420.5(PCDH1):​c.2250T>C​(p.Ala750Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,612,390 control chromosomes in the GnomAD database, including 106,263 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 0.35 (9799 hom., cov: 32)
  • Exomes 𝑓: 0.36 (96464 hom.)
• Consequence: PCDH1 NM_032420.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 22 publications found

Genes affected

PCDH1 (HGNC:8655): (protocadherin 1) This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.971 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032420.5. 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
	PCDH1	NM_032420.5	MANE Select	c.2250T>C	p.Ala750Ala	synonymous	Exon 3 of 5	NP_115796.2
	PCDH1	NM_001278613.2		c.2298T>C	p.Ala766Ala	synonymous	Exon 3 of 3	NP_001265542.1
	PCDH1	NM_002587.5		c.2250T>C	p.Ala750Ala	synonymous	Exon 3 of 3	NP_002578.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH1	ENST00000287008.8	TSL:5 MANE Select	c.2250T>C	p.Ala750Ala	synonymous	Exon 3 of 5	ENSP00000287008.3
	PCDH1	ENST00000394536.4	TSL:1	c.2250T>C	p.Ala750Ala	synonymous	Exon 3 of 3	ENSP00000378043.3
	PCDH1	ENST00000511044.1	TSL:1	n.1478T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53513 AN: 151908 Hom.: 9778 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.385

GnomAD2 exomes AF: 0.390 AC: 97172 AN: 249408 AF XY: 0.400

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.344

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.563

Gnomad FIN exome AF: 0.322

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.389

GnomAD4 exome AF: 0.357 AC: 521484 AN: 1460364 Hom.: 96464 Cov.: 47 AF XY: 0.364 AC XY: 264465 AN XY: 726236

African (AFR) AF: 0.316 AC: 10582 AN: 33456

American (AMR) AF: 0.351 AC: 15676 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 11712 AN: 26106

East Asian (EAS) AF: 0.556 AC: 22044 AN: 39648

South Asian (SAS) AF: 0.550 AC: 47440 AN: 86212

European-Finnish (FIN) AF: 0.319 AC: 16982 AN: 53314

Middle Eastern (MID) AF: 0.446 AC: 2570 AN: 5766

European-Non Finnish (NFE) AF: 0.335 AC: 371647 AN: 1110890

Other (OTH) AF: 0.378 AC: 22831 AN: 60324

GnomAD4 genome AF: 0.352 AC: 53559 AN: 152026 Hom.: 9799 Cov.: 32 AF XY: 0.360 AC XY: 26726 AN XY: 74330

African (AFR) AF: 0.314 AC: 13017 AN: 41466

American (AMR) AF: 0.368 AC: 5622 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3472

East Asian (EAS) AF: 0.572 AC: 2948 AN: 5150

South Asian (SAS) AF: 0.563 AC: 2719 AN: 4828

European-Finnish (FIN) AF: 0.316 AC: 3338 AN: 10576

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23058 AN: 67926

Other (OTH) AF: 0.391 AC: 826 AN: 2112

Alfa AF: 0.364 Hom.: 10196

Bravo AF: 0.352

Asia WGS AF: 0.547 AC: 1905 AN: 3478

EpiCase AF: 0.372

EpiControl AF: 0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.61
PhyloP100		-0.97
Mutation Taster		=97/3	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: rs3797054; hg19: chr5-141243646; COSMIC: COSV54612266; COSMIC: COSV54612266;