rs35411582

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_019604.4(CRTAM):c.47A>C(p.Glu16Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,602,386 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 14 hom. )

Consequence

CRTAM
NM_019604.4 missense, splice_region

Scores

Splicing: ADA: 0.00007565

Clinical Significance

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

Conservation

PhyloP100: 0.509

Publications

2 publications found

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:

ENSG00000285909 (HGNC:):

ENSG00000285909 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002638787).

BP6

Variant 11-122850068-A-C is Benign according to our data. Variant chr11-122850068-A-C is described in ClinVar as Benign. ClinVar VariationId is 781238.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 = 0.00793 (1208/152282) while in subpopulation AFR AF = 0.0279 (1159/41560). AF 95% confidence interval is 0.0266. There are 18 homozygotes in GnomAd4. There are 576 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019604.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAM	NM_019604.4	MANE Select	c.47A>C	p.Glu16Ala	missense splice_region	Exon 2 of 10	NP_062550.2	O95727-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRTAM	ENST00000227348.9	TSL:1 MANE Select	c.47A>C	p.Glu16Ala	missense splice_region	Exon 2 of 10	ENSP00000227348.4	O95727-1
CRTAM	ENST00000910133.1		c.47A>C	p.Glu16Ala	missense splice_region	Exon 3 of 11	ENSP00000580192.1
ENSG00000285909	ENST00000649590.1		n.73+1477T>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

1202

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00222

AC:

553

AN:

249384

AF XY:

0.00168

show subpopulations

Gnomad AFR exome

AF:

0.0314

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000759

AC:

1100

AN:

1450104

Hom.:

Cov.:

AF XY:

0.000661

AC XY:

476

AN XY:

720056

show subpopulations

African (AFR)

AF:

0.0275

AC:

914

AN:

33252

American (AMR)

AF:

0.00131

AC:

AN:

44200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25880

East Asian (EAS)

AF:

0.00

AC:

AN:

39446

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53180

Middle Eastern (MID)

AF:

0.000622

AC:

AN:

4822

European-Non Finnish (NFE)

AF:

0.0000317

AC:

AN:

1104338

Other (OTH)

AF:

0.00149

AC:

AN:

59780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

104

155

207

259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00793

AC:

1208

AN:

152282

Hom.:

Cov.:

AF XY:

0.00773

AC XY:

576

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0279

AC:

1159

AN:

41560

American (AMR)

AF:

0.00222

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68002

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

126

188

251

314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00352

Hom.:

Bravo

AF:

0.00934

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0277

AC:

122

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00270

AC:

328

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.023

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

0.51

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.39

REVEL

Benign

0.054

Sift

Benign

0.35

Sift4G

Benign

0.75

Polyphen

0.0010

Vest4

0.20

MVP

0.21

MPC

0.074

ClinPred

0.0027

GERP RS

-0.34

Varity_R

0.041

gMVP

0.59

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000076

dbscSNV1_RF

Benign

0.022

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over