rs2272094

Variant names:

• chr11-122867553-A-G
• rs2272094
• NM_019604.4:c.962A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-122867553-A-G
• chr11-122867553-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019604.4(CRTAM):​c.962A>G​(p.Lys321Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 1,612,130 control chromosomes in the GnomAD database, including 396,566 homozygotes. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (31001 hom., cov: 31)
  • Exomes 𝑓: 0.70 (365565 hom.)
• Consequence: CRTAM NM_019604.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001475
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672
• Publications: 40 publications found

Genes affected

CRTAM (HGNC:24313): (cytotoxic and regulatory T cell molecule) The CRTAM gene is upregulated in CD4 (see MIM 186940)-positive and CD8 (see CD8A; MIM 186910)-positive T cells and encodes a type I transmembrane protein with V and C1-like Ig domains (Yeh et al., 2008 [PubMed 18329370]).[supplied by OMIM, Feb 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.602893E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRTAM	NM_019604.4	c.962A>G	p.Lys321Arg	missense_variant, splice_region_variant	Exon 8 of 10	ENST00000227348.9	NP_062550.2
CRTAM	NM_001304782.2	c.365A>G	p.Lys122Arg	missense_variant, splice_region_variant	Exon 3 of 5		NP_001291711.1
CRTAM	XM_011542900.3	c.809A>G	p.Lys270Arg	missense_variant, splice_region_variant	Exon 7 of 9		XP_011541202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRTAM	ENST00000227348.9	c.962A>G	p.Lys321Arg	missense_variant, splice_region_variant	Exon 8 of 10	1	NM_019604.4	ENSP00000227348.4
CRTAM	ENST00000533709.1	c.365A>G	p.Lys122Arg	missense_variant, splice_region_variant	Exon 3 of 5	1		ENSP00000433728.1
CRTAM	ENST00000533416.1	n.274A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94390 AN: 151828 Hom.: 30990 Cov.: 31

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.666

GnomAD2 exomes AF: 0.674 AC: 168765 AN: 250260 AF XY: 0.680

Gnomad AFR exome AF: 0.404

Gnomad AMR exome AF: 0.748

Gnomad ASJ exome AF: 0.756

Gnomad EAS exome AF: 0.444

Gnomad FIN exome AF: 0.686

Gnomad NFE exome AF: 0.727

Gnomad OTH exome AF: 0.706

GnomAD4 exome AF: 0.704 AC: 1028016 AN: 1460184 Hom.: 365565 Cov.: 43 AF XY: 0.703 AC XY: 510776 AN XY: 726272

African (AFR) AF: 0.402 AC: 13449 AN: 33414

American (AMR) AF: 0.746 AC: 33175 AN: 44462

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 19692 AN: 26096

East Asian (EAS) AF: 0.499 AC: 19782 AN: 39676

South Asian (SAS) AF: 0.639 AC: 54977 AN: 86026

European-Finnish (FIN) AF: 0.691 AC: 36866 AN: 53376

Middle Eastern (MID) AF: 0.789 AC: 4538 AN: 5754

European-Non Finnish (NFE) AF: 0.724 AC: 804022 AN: 1111066

Other (OTH) AF: 0.688 AC: 41515 AN: 60314

GnomAD4 genome AF: 0.621 AC: 94421 AN: 151946 Hom.: 31001 Cov.: 31 AF XY: 0.619 AC XY: 45953 AN XY: 74252

African (AFR) AF: 0.415 AC: 17191 AN: 41438

American (AMR) AF: 0.704 AC: 10744 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2370 AN: 5150

South Asian (SAS) AF: 0.621 AC: 2985 AN: 4806

European-Finnish (FIN) AF: 0.683 AC: 7190 AN: 10526

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49175 AN: 67976

Other (OTH) AF: 0.658 AC: 1392 AN: 2114

Alfa AF: 0.700 Hom.: 126823

Bravo AF: 0.616

TwinsUK AF: 0.732 AC: 2713

ALSPAC AF: 0.727 AC: 2802

ESP6500AA AF: 0.421 AC: 1855

ESP6500EA AF: 0.724 AC: 6226

ExAC AF: 0.666 AC: 80870

Asia WGS AF: 0.513 AC: 1783 AN: 3478

EpiCase AF: 0.738

EpiControl AF: 0.735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.4
DANN	Benign	0.85
DEOGEN2	Benign	0.057	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.56	T;T
MetaRNN	Benign	0.0000016	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.33	N;.
PhyloP100		0.67
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.046
Sift	Benign	0.62	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.058	B;B
Vest4		0.022
MPC		0.064
ClinPred		0.00061	T
GERP RS		-2.5
Varity_R		0.034
gMVP		0.19
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2272094; hg19: chr11-122738261; COSMIC: COSV107317254;