Variant rs2272094 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 16/22 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

Variant links:

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]

CRTAM links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE
CRTAM	NM_019604.4 linkuse as main transcript	c.962A>G	p.Lys321Arg	missense_variant, splice_region_variant	8/10	ENST00000227348.9
CRTAM	NM_001304782.2 linkuse as main transcript	c.365A>G	p.Lys122Arg	missense_variant, splice_region_variant	3/5
CRTAM	XM_011542900.3 linkuse as main transcript	c.809A>G	p.Lys270Arg	missense_variant, splice_region_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRTAM	ENST00000227348.9 linkuse as main transcript	c.962A>G	p.Lys321Arg	missense_variant, splice_region_variant	8/10	1	NM_019604.4	P1	O95727-1
CRTAM	ENST00000533709.1 linkuse as main transcript	c.365A>G	p.Lys122Arg	missense_variant, splice_region_variant	3/5	1			O95727-2
CRTAM	ENST00000533416.1 linkuse as main transcript	n.274A>G		splice_region_variant, non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.622

AC:

94390

AN:

151828

Hom.:

30990

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.674

AC:

168765

AN:

250260

Hom.:

58439

AF XY:

0.680

AC XY:

91989

AN XY:

135252

show subpopulations

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 SAS exome

AF:

0.638

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.:

AF XY:

0.703

AC XY:

510776

AN XY:

726272

show subpopulations

Gnomad4 AFR exome

AF:

0.402

Gnomad4 AMR exome

AF:

0.746

Gnomad4 ASJ exome

AF:

0.755

Gnomad4 EAS exome

AF:

0.499

Gnomad4 SAS exome

AF:

0.639

Gnomad4 FIN exome

AF:

0.691

Gnomad4 NFE exome

AF:

0.724

Gnomad4 OTH exome

AF:

0.688

GnomAD4 genome

AF:

0.621

AC:

94421

AN:

151946

Hom.:

31001

Cov.:

AF XY:

0.619

AC XY:

45953

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.415

Gnomad4 AMR

AF:

0.704

Gnomad4 ASJ

AF:

0.756

Gnomad4 EAS

AF:

0.460

Gnomad4 SAS

AF:

0.621

Gnomad4 FIN

AF:

0.683

Gnomad4 NFE

AF:

0.723

Gnomad4 OTH

AF:

0.658

Alfa

AF:

0.707

Hom.:

95509

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

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

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0000016

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.33

N;.

MutationTaster

Benign

0.019

P;P

PrimateAI

Benign

0.37

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

GERP RS

-2.5

Varity_R

0.034

gMVP

0.19

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over