1-158256783-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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

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 -14 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_single_submitter, 1 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 GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD1A	NM_001763.3	c.605-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000289429.6
CD1A	NM_001320652.2	c.572-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
CD1A	XM_024450738.2	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	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.: 23 Cov.: 32

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.: 9 AF XY: 0.00192 AC XY: 260 AN XY: 135288

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.: 34 Cov.: 32 AF XY: 0.000914 AC XY: 664 AN XY: 726826

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.: 23 Cov.: 32 AF XY: 0.0109 AC XY: 813 AN XY: 74456

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.: 6

Bravo AF: 0.0117

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 30, 2017

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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

Other links and lift over

dbSNP: rs148563016; hg19: chr1-158226573;