Variant 11-122855722-A-G 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 ENST00000227348.9(CRTAM):c.518A>G(p.Asp173Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00266 in 1,614,064 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.014 ( 59 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 67 hom. )

Consequence

CRTAM
ENST00000227348.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.41

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=0.0051965714).

BP6

Variant 11-122855722-A-G is Benign according to our data. Variant chr11-122855722-A-G is described in ClinVar as [Benign]. Clinvar id is 778566.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 = 0.0137 (2093/152286) while in subpopulation AFR AF= 0.0478 (1985/41552). AF 95% confidence interval is 0.046. There are 59 homozygotes in gnomad4. There are 997 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRTAM	NM_019604.4 linkuse as main transcript	c.518A>G	p.Asp173Gly	missense_variant	5/10	ENST00000227348.9	NP_062550.2
CRTAM	XM_011542900.3 linkuse as main transcript	c.365A>G	p.Asp122Gly	missense_variant	4/9		XP_011541202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRTAM	ENST00000227348.9 linkuse as main transcript	c.518A>G	p.Asp173Gly	missense_variant	5/10	1	NM_019604.4	ENSP00000227348	P1	O95727-1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2090

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0478

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00380

AC:

954

AN:

251274

Hom.:

AF XY:

0.00267

AC XY:

363

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.0502

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00150

AC:

2198

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

924

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0520

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000935

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.0137

AC:

2093

AN:

152286

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

997

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0478

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00543

Hom.:

Bravo

AF:

0.0161

ESP6500AA

AF:

0.0475

AC:

209

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00475

AC:

577

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

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

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.14

Sift

Uncertain

0.013

Sift4G

Uncertain

0.040

Polyphen

0.99

Vest4

0.52

MVP

0.35

MPC

0.42

ClinPred

0.037

GERP RS

4.9

Varity_R

0.38

gMVP

0.66

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

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