chr1-158255293-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001763.3(CD1A):c.268C>T(p.Arg90Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,614,082 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 27 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 34 hom. )

Consequence

CD1A
NM_001763.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.464

Variant links:

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]

CD1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026014745).

BP6

Variant 1-158255293-C-T is Benign according to our data. Variant chr1-158255293-C-T is described in ClinVar as [Benign]. Clinvar id is 785843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1763/152242) while in subpopulation AFR AF= 0.0398 (1654/41540). AF 95% confidence interval is 0.0382. There are 27 homozygotes in gnomad4. There are 843 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1A	NM_001763.3 link	c.268C>T	p.Arg90Cys	missense_variant	Exon 2 of 6	ENST00000289429.6	NP_001754.2	P06126
CD1A	XM_024450738.2 link	c.-201C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 7		XP_024306506.1
CD1A	NM_001320652.2 link	c.235C>T	p.Arg79Cys	missense_variant	Exon 2 of 6		NP_001307581.1	P06126
CD1A	XM_024450738.2 link	c.-201C>T		5_prime_UTR_variant	Exon 3 of 7		XP_024306506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1A	ENST00000289429.6 link	c.268C>T	p.Arg90Cys	missense_variant	Exon 2 of 6	1	NM_001763.3	ENSP00000289429.5		P06126

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1746

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00768

GnomAD3 exomes

AF:

0.00336

AC:

844

AN:

250818

Hom.:

AF XY:

0.00254

AC XY:

344

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.0400

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000610

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00140

AC:

2052

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

923

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0389

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00513

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000300

Gnomad4 OTH exome

AF:

0.00258

GnomAD4 genome

AF:

0.0116

AC:

1763

AN:

152242

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

843

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0398

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00760

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.0123

ESP6500AA

AF:

0.0402

AC:

177

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00390

AC:

474

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 30, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.083

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00023

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.41

PrimateAI

Benign

0.26

PROVEAN

Benign

0.020

REVEL

Benign

0.034

Sift

Benign

0.034

Sift4G

Uncertain

0.024

Polyphen

0.0020

Vest4

0.060

MVP

0.13

MPC

0.043

ClinPred

0.0095

GERP RS

-3.3

Varity_R

0.24

gMVP

0.40

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over