NM_001763.3:c.719G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001763.3(CD1A):c.719G>A(p.Gly240Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 1,614,210 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G240S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

CD1A
NM_001763.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.888

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008817434).

BP6

Variant 1-158256900-G-A is Benign according to our data. Variant chr1-158256900-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 712089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1A	NM_001763.3 link	c.719G>A	p.Gly240Asp	missense_variant	Exon 4 of 6	ENST00000289429.6	NP_001754.2	P06126
CD1A	NM_001320652.2 link	c.686G>A	p.Gly229Asp	missense_variant	Exon 4 of 6		NP_001307581.1	P06126
CD1A	XM_024450738.2 link	c.251G>A	p.Gly84Asp	missense_variant	Exon 5 of 7		XP_024306506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1A	ENST00000289429.6 link	c.719G>A	p.Gly240Asp	missense_variant	Exon 4 of 6	1	NM_001763.3	ENSP00000289429.5		P06126

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

428

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00453

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00284

AC:

714

AN:

251492

Hom.:

AF XY:

0.00288

AC XY:

392

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00418

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00377

AC:

5506

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

2774

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00601

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00143

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.00430

Gnomad4 OTH exome

AF:

0.00369

GnomAD4 genome

AF:

0.00280

AC:

427

AN:

152328

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00453

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.00285

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.00270

AC:

328

EpiCase

AF:

0.00567

EpiControl

AF:

0.00593

ClinVar

Significance: Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.21

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.65

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.78

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.037

Sift

Benign

0.041

Sift4G

Uncertain

0.028

Polyphen

0.37

Vest4

0.20

MVP

0.25

MPC

0.20

ClinPred

0.047

GERP RS

0.89

Varity_R

0.28

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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