Variant chr1-158256783-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001763.3(CD1A):c.605-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,613,446 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts 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 Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 34 hom. )

Consequence

CD1A
NM_001763.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008776

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.145

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 (BayesDel_noAF=-0.79).

BP6

Variant 1-158256783-C-T is Benign according to our data. Variant chr1-158256783-C-T is described in ClinVar as [Benign]. Clinvar id is 785844.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 = 0.011 (1682/152290) while in subpopulation AFR AF= 0.0388 (1611/41556). AF 95% confidence interval is 0.0372. There are 23 homozygotes in gnomad4. There are 813 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CD1A	NM_001763.3 linkuse as main transcript	c.605-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000289429.6
CD1A	NM_001320652.2 linkuse as main transcript	c.572-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
CD1A	XM_024450738.2 linkuse as main transcript	c.137-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1A	ENST00000289429.6 linkuse as main transcript	c.605-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001763.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1670

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00276

AC:

691

AN:

250342

Hom.:

AF XY:

0.00192

AC XY:

260

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.0385

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00109

AC:

1592

AN:

1461156

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

664

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.0384

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.0110

AC:

1682

AN:

152290

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

813

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0388

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00539

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 30, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.2

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00088

dbscSNV1_RF

Benign

0.096

SpliceAI score (max)

0.080

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