Variant 11-122864660-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_019604.4(CRTAM):c.758C>T(p.Thr253Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,613,358 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 37 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 28 hom. )

Consequence

CRTAM
NM_019604.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.462

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019713044).

BP6

Variant 11-122864660-C-T is Benign according to our data. Variant chr11-122864660-C-T is described in ClinVar as [Benign]. Clinvar id is 784223.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 = 0.00931 (1418/152294) while in subpopulation AFR AF= 0.0317 (1317/41562). AF 95% confidence interval is 0.0303. There are 37 homozygotes in gnomad4. There are 673 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CRTAM	NM_019604.4 linkuse as main transcript	c.758C>T	p.Thr253Ile	missense_variant	7/10	ENST00000227348.9	NP_062550.2
CRTAM	NM_001304782.2 linkuse as main transcript	c.161C>T	p.Thr54Ile	missense_variant	2/5		NP_001291711.1
CRTAM	XM_011542900.3 linkuse as main transcript	c.605C>T	p.Thr202Ile	missense_variant	6/9		XP_011541202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAM	ENST00000227348.9 linkuse as main transcript	c.758C>T	p.Thr253Ile	missense_variant	7/10	1	NM_019604.4	ENSP00000227348	P1	O95727-1
CRTAM	ENST00000533709.1 linkuse as main transcript	c.161C>T	p.Thr54Ile	missense_variant	2/5	1		ENSP00000433728		O95727-2
CRTAM	ENST00000533416.1 linkuse as main transcript	n.70C>T		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes

AF:

0.00932

AC:

1418

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00259

AC:

651

AN:

251062

Hom.:

AF XY:

0.00189

AC XY:

257

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000941

AC:

1375

AN:

1461064

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

576

AN XY:

726926

show subpopulations

Gnomad4 AFR exome

AF:

0.0319

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000882

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00931

AC:

1418

AN:

152294

Hom.:

Cov.:

AF XY:

0.00904

AC XY:

673

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00158

Hom.:

Bravo

AF:

0.0100

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0329

AC:

145

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00320

AC:

389

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.9

DANN

Uncertain

0.98

DEOGEN2

Benign

0.056

T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.056

Sift

Benign

0.57

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0020

B;B

Vest4

0.29

MVP

0.28

MPC

0.073

ClinPred

0.0037

GERP RS

-0.33

Varity_R

0.038

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over