rs4151676

Variant names:

• chr5-140786033-G-A
• rs4151676
• ENST00000655235.1:n.3479C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000655235.1(ENSG00000279726):​n.3479C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 383,986 control chromosomes in the GnomAD database, including 80 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 0.015 (64 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (16 hom.)
• Consequence: ENSG00000279726 ENST00000655235.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544

Genes affected

ENSG00000279726 (HGNC:):

PCDHA1 (HGNC:8663): (protocadherin alpha 1) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. 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 connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDHA1	NM_018900.4	c.-258G>A		upstream_gene_variant		ENST00000504120.4	NP_061723.1
PCDHA1	NM_031410.2	c.-258G>A		upstream_gene_variant			NP_113598.1
PCDHA1	NM_031411.3	c.-258G>A		upstream_gene_variant			NP_113599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000279726	ENST00000655235.1	n.3479C>T		non_coding_transcript_exon_variant	Exon 2 of 2
PCDHA1	ENST00000504120.4	c.-258G>A		upstream_gene_variant		1	NM_018900.4	ENSP00000420840.3
PCDHA1	ENST00000378133.4	c.-258G>A		upstream_gene_variant		6		ENSP00000367373.3

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2309 AN: 152136 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00621

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00239 AC: 553 AN: 231732 Hom.: 16 AF XY: 0.00201 AC XY: 239 AN XY: 118836

Gnomad4 AFR exome AF: 0.0513

Gnomad4 AMR exome AF: 0.00553

Gnomad4 ASJ exome AF: 0.000131

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000412

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000242

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.0152 AC: 2320 AN: 152254 Hom.: 64 Cov.: 33 AF XY: 0.0149 AC XY: 1110 AN XY: 74442

Gnomad4 AFR AF: 0.0522

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0130 Hom.: 6

Bravo AF: 0.0175

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4151676; hg19: chr5-140165618;