1-158328922-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001764.3(CD1B):c.979C>T(p.Arg327Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000507 in 1,596,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CD1B
NM_001764.3 missense, splice_region

Scores

Splicing: ADA: 0.001602

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018787682).

BP6

Variant 1-158328922-G-A is Benign according to our data. Variant chr1-158328922-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3140384.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1B	NM_001764.3 link	c.979C>T	p.Arg327Trp	missense_variant, splice_region_variant	Exon 5 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.979C>T	p.Arg327Trp	missense_variant, splice_region_variant	Exon 5 of 6	1	NM_001764.3	ENSP00000357150.3		P29016-1
CD1B	ENST00000451207.5 link	c.715C>T	p.Arg239Trp	missense_variant, splice_region_variant	Exon 4 of 5	3		ENSP00000395161.1		H7C0I2

Frequencies

GnomAD3 genomes

AF:

0.0000528

AC:

AN:

151620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000737

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000634

AC:

AN:

236458

Hom.:

AF XY:

0.0000860

AC XY:

AN XY:

127844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000578

Gnomad SAS exome

AF:

0.0000745

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000505

AC:

AN:

1444852

Hom.:

Cov.:

AF XY:

0.0000487

AC XY:

AN XY:

718660

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000244

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000606

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151730

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000737

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000109

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000165

EpiControl

AF:

0.000298

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 20, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.6

DANN

Benign

0.68

DEOGEN2

Benign

0.039

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.32

M_CAP

Benign

0.0030

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.66

PrimateAI

Benign

0.23

PROVEAN

Benign

4.3

REVEL

Benign

0.079

Sift

Benign

0.037

Sift4G

Uncertain

0.053

Polyphen

0.010

Vest4

0.24

MVP

0.18

MPC

0.015

ClinPred

0.092

GERP RS

-8.5

Varity_R

0.054

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.33

SpliceAI score (max)

0.030

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