11-122864660-C-T

Variant names:

• chr11-122864660-C-T
• rs75065751
• NM_019604.4:c.758C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 14/21 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.462
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 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.758C>T	p.Thr253Ile	missense	Exon 7 of 10	NP_062550.2	O95727-1
	CRTAM	NM_001304782.2		c.161C>T	p.Thr54Ile	missense	Exon 2 of 5	NP_001291711.1	O95727-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAM	ENST00000227348.9	TSL:1 MANE Select	c.758C>T	p.Thr253Ile	missense	Exon 7 of 10	ENSP00000227348.4	O95727-1
	CRTAM	ENST00000533709.1	TSL:1	c.161C>T	p.Thr54Ile	missense	Exon 2 of 5	ENSP00000433728.1	O95727-2
	CRTAM	ENST00000910133.1		c.758C>T	p.Thr253Ile	missense	Exon 8 of 11	ENSP00000580192.1

Frequencies

GnomAD3 genomes AF: 0.00932 AC: 1418 AN: 152176 Hom.: 37 Cov.: 32

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

GnomAD2 exomes AF: 0.00259 AC: 651 AN: 251062 AF XY: 0.00189

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 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.: 28 Cov.: 29 AF XY: 0.000792 AC XY: 576 AN XY: 726926

African (AFR) AF: 0.0319 AC: 1068 AN: 33428

American (AMR) AF: 0.00248 AC: 111 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000882 AC: 98 AN: 1111412

Other (OTH) AF: 0.00149 AC: 90 AN: 60356

GnomAD4 genome AF: 0.00931 AC: 1418 AN: 152294 Hom.: 37 Cov.: 32 AF XY: 0.00904 AC XY: 673 AN XY: 74452

African (AFR) AF: 0.0317 AC: 1317 AN: 41562

American (AMR) AF: 0.00510 AC: 78 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68022

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00339 Hom.: 14

Bravo AF: 0.0100

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0329 AC: 145

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00320 AC: 389

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.54	T
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	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.46
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.056
Sift	Benign	0.57	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.29
MVP		0.28
MPC		0.073
ClinPred		0.0037	T
GERP RS		-0.33
Varity_R		0.038
gMVP		0.39
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs75065751; hg19: chr11-122735368;