1-158256900-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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 (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (17 hom.)
• Consequence: CD1A NM_001763.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.888

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 -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD1A	NM_001763.3	c.719G>A	p.Gly240Asp	missense_variant	4/6	ENST00000289429.6
CD1A	NM_001320652.2	c.686G>A	p.Gly229Asp	missense_variant	4/6
CD1A	XM_024450738.2	c.251G>A	p.Gly84Asp	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1A	ENST00000289429.6	c.719G>A	p.Gly240Asp	missense_variant	4/6	1	NM_001763.3	P1

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 428 AN: 152210 Hom.: 1 Cov.: 32

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.: 6 AF XY: 0.00288 AC XY: 392 AN XY: 135920

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.: 17 Cov.: 33 AF XY: 0.00381 AC XY: 2774 AN XY: 727242

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.: 1 Cov.: 32 AF XY: 0.00266 AC XY: 198 AN XY: 74476

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.: 0

Bravo AF: 0.00285

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00326 AC: 28

ExAC AF: 0.00270 AC: 328

EpiCase AF: 0.00567

EpiControl AF: 0.00593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	18
Dann	Benign	0.94
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.78	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.037
Sift	Benign	0.041	D
Sift4G	Uncertain	0.028	D
Polyphen		0.37	B
Vest4		0.20
MVP		0.25
MPC		0.20
ClinPred		0.047	T
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

Other links and lift over

dbSNP: rs141060322; hg19: chr1-158226690; COSMIC: COSV56860244;