1-158329517-C-T

Variant names:

Variant summary

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

The NM_001764.3(CD1B):c.739G>A(p.Gly247Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,614,142 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 16 hom. )

Consequence

CD1B
NM_001764.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.315

Variant links:

Genes affected

CD1B (HGNC:1635): (CD1b 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 late endosomes and lysosomes via a tyrosine-based motif in the cytoplasmic tail, and requires vesicular acidification to bind lipid antigens. [provided by RefSeq, Jul 2008]

CD1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036280155).

BP6

Variant 1-158329517-C-T is Benign according to our data. Variant chr1-158329517-C-T is described in ClinVar as [Benign]. Clinvar id is 775614.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 = 0.0099 (1507/152248) while in subpopulation AFR AF= 0.0331 (1375/41540). AF 95% confidence interval is 0.0316. There are 24 homozygotes in gnomad4. There are 700 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1B	NM_001764.3 link	c.739G>A	p.Gly247Ser	missense_variant	Exon 4 of 6	ENST00000368168.4	NP_001755.1	P29016-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1B	ENST00000368168.4 link	c.739G>A	p.Gly247Ser	missense_variant	Exon 4 of 6	1	NM_001764.3	ENSP00000357150.3		P29016-1
CD1B	ENST00000451207.5 link	c.622+18G>A		intron_variant	Intron 3 of 4	3		ENSP00000395161.1		H7C0I2

Frequencies

GnomAD3 genomes

AF:

0.00987

AC:

1502

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00274

AC:

688

AN:

251470

Hom.:

AF XY:

0.00196

AC XY:

267

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0339

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00111

AC:

1622

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000986

AC XY:

717

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0322

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00990

AC:

1507

AN:

152248

Hom.:

Cov.:

AF XY:

0.00940

AC XY:

700

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0331

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.0113

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0356

AC:

157

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00327

AC:

397

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.090

Sift

Benign

0.042

Sift4G

Uncertain

0.036

Polyphen

0.69

Vest4

0.067

MVP

0.20

MPC

0.071

ClinPred

0.045

GERP RS

4.3

Varity_R

0.48

gMVP

0.60

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

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