11-122850068-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_019604.4(CRTAM):ā€‹c.47A>Cā€‹(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. 17/22 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 (ā˜…ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.0079 ( 18 hom., cov: 32)
Exomes š‘“: 0.00076 ( 14 hom. )

Consequence

CRTAM
NM_019604.4 missense, splice_region

Scores

18
Splicing: ADA: 0.00007565
2

Clinical Significance

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

Conservation

PhyloP100: 0.509
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]

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=0.002638787).
BP6
Variant 11-122850068-A-C is Benign according to our data. Variant chr11-122850068-A-C is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRTAMNM_019604.4 linkuse as main transcriptc.47A>C p.Glu16Ala missense_variant, splice_region_variant 2/10 ENST00000227348.9 NP_062550.2
CRTAMXM_011542900.3 linkuse as main transcriptc.47A>C p.Glu16Ala missense_variant, splice_region_variant 2/9 XP_011541202.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRTAMENST00000227348.9 linkuse as main transcriptc.47A>C p.Glu16Ala missense_variant, splice_region_variant 2/101 NM_019604.4 ENSP00000227348 P1O95727-1
ENST00000649590.1 linkuse as main transcriptn.73+1477T>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00790
AC:
1202
AN:
152164
Hom.:
18
Cov.:
32
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
GnomAD3 exomes
AF:
0.00222
AC:
553
AN:
249384
Hom.:
11
AF XY:
0.00168
AC XY:
227
AN XY:
134794
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 SAS 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.:
14
Cov.:
31
AF XY:
0.000661
AC XY:
476
AN XY:
720056
show subpopulations
Gnomad4 AFR exome
AF:
0.0275
Gnomad4 AMR exome
AF:
0.00131
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000317
Gnomad4 OTH exome
AF:
0.00149
GnomAD4 genome
AF:
0.00793
AC:
1208
AN:
152282
Hom.:
18
Cov.:
32
AF XY:
0.00773
AC XY:
576
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0279
Gnomad4 AMR
AF:
0.00222
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00193
Hom.:
5
Bravo
AF:
0.00934
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0277
AC:
122
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00270
AC:
328
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 29, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
13
DANN
Benign
0.93
DEOGEN2
Benign
0.023
T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.50
T
MetaRNN
Benign
0.0026
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.39
N
REVEL
Benign
0.054
Sift
Benign
0.35
T
Sift4G
Benign
0.75
T
Polyphen
0.0010
B
Vest4
0.20
MVP
0.21
MPC
0.074
ClinPred
0.0027
T
GERP RS
-0.34
Varity_R
0.041
gMVP
0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35411582; hg19: chr11-122720776; API