chr1-158255606-G-T

Position:

• chr1-158255606-G-T

Variant summary

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

The NM_001763.3(CD1A):​c.325+256G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,886 control chromosomes in the GnomAD database, including 13,824 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 0.40 (13824 hom., cov: 31)
• Consequence: CD1A NM_001763.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

Genes affected

CD1A (HGNC:1634): (CD1a molecule) This gene encodes a member of the CD1 family of transmembrane glycoproteins, which are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. The protein encoded by this gene localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD1A	NM_001763.3	c.325+256G>T		intron_variant		ENST00000289429.6	NP_001754.2
CD1A	NM_001320652.2	c.292+256G>T		intron_variant			NP_001307581.1
CD1A	XM_024450738.2	c.-144+256G>T		intron_variant			XP_024306506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD1A	ENST00000289429.6	c.325+256G>T		intron_variant		1	NM_001763.3	ENSP00000289429	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61036 AN: 151768 Hom.: 13800 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.367

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.402 AC: 61112 AN: 151886 Hom.: 13824 Cov.: 31 AF XY: 0.406 AC XY: 30125 AN XY: 74230

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.371

Alfa AF: 0.365 Hom.: 1671

Bravo AF: 0.407

Asia WGS AF: 0.609 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs440419; hg19: chr1-158225396;