chr1-158256920-A-T

Variant names:

• chr1-158256920-A-T
• NM_001763.3:c.739A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001763.3(CD1A):​c.739A>T​(p.Thr247Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T247P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD1A NM_001763.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20252764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1A	NM_001763.3	c.739A>T	p.Thr247Ser	missense_variant	Exon 4 of 6	ENST00000289429.6	NP_001754.2
CD1A	NM_001320652.2	c.706A>T	p.Thr236Ser	missense_variant	Exon 4 of 6		NP_001307581.1
CD1A	XM_024450738.2	c.271A>T	p.Thr91Ser	missense_variant	Exon 5 of 7		XP_024306506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1A	ENST00000289429.6	c.739A>T	p.Thr247Ser	missense_variant	Exon 4 of 6	1	NM_001763.3	ENSP00000289429.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Uncertain	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.032
Sift	Benign	0.039	D
Sift4G	Uncertain	0.040	D
Polyphen		0.95	P
Vest4		0.18
MutPred		0.55		Gain of disorder (P = 0.0696);
MVP		0.25
MPC		0.25
ClinPred		0.46	T
GERP RS		1.3
Varity_R		0.29
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-158226710;