11-122850068-A-C

Position:

• chr11-122850068-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000227348.9(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. 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0079 (18 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (14 hom.)
• Consequence: CRTAM ENST00000227348.9 missense, splice_region
• Scores: Splicing: ADA: 0.00007565
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.509

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]

(HGNC:):

ACMG classification

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
CRTAM	NM_019604.4	c.47A>C	p.Glu16Ala	missense_variant, splice_region_variant	2/10	ENST00000227348.9	NP_062550.2
CRTAM	XM_011542900.3	c.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
CRTAM	ENST00000227348.9	c.47A>C	p.Glu16Ala	missense_variant, splice_region_variant	2/10	1	NM_019604.4	ENSP00000227348	P1
	ENST00000649590.1	n.73+1477T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00790 AC: 1202 AN: 152164 Hom.: 18 Cov.: 32

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

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

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

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

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	Jun 29, 2018	- -

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

Other links and lift over

dbSNP: rs35411582; hg19: chr11-122720776;