chr11-122851732-C-A

Variant names:

• chr11-122851732-C-A
• rs34397316
• NM_019604.4:c.233C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019604.4(CRTAM):​c.233C>A​(p.Ala78Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,614,088 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (239 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (203 hom.)
• Consequence: CRTAM NM_019604.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.746
• Publications: 6 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]

ENSG00000285909 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.002107352).
• BP6: Variant 11-122851732-C-A is Benign according to our data. Variant chr11-122851732-C-A is described in ClinVar as Benign. ClinVar VariationId is 776673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

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.233C>A	p.Ala78Asp	missense	Exon 3 of 10	NP_062550.2	O95727-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTAM	ENST00000227348.9	TSL:1 MANE Select	c.233C>A	p.Ala78Asp	missense	Exon 3 of 10	ENSP00000227348.4	O95727-1
	CRTAM	ENST00000910133.1		c.233C>A	p.Ala78Asp	missense	Exon 4 of 11	ENSP00000580192.1
	ENSG00000285909	ENST00000649590.1		n.-115G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4831 AN: 152150 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.00819 AC: 2058 AN: 251380 AF XY: 0.00620

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.00538

Gnomad ASJ exome AF: 0.00188

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00325 AC: 4744 AN: 1461820 Hom.: 203 Cov.: 31 AF XY: 0.00276 AC XY: 2004 AN XY: 727216

African (AFR) AF: 0.111 AC: 3702 AN: 33470

American (AMR) AF: 0.00639 AC: 286 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 61 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5768

European-Non Finnish (NFE) AF: 0.000210 AC: 234 AN: 1111962

Other (OTH) AF: 0.00687 AC: 415 AN: 60396

GnomAD4 genome AF: 0.0318 AC: 4848 AN: 152268 Hom.: 239 Cov.: 32 AF XY: 0.0307 AC XY: 2283 AN XY: 74452

African (AFR) AF: 0.110 AC: 4581 AN: 41530

American (AMR) AF: 0.0119 AC: 182 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68034

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.0117 Hom.: 194

Bravo AF: 0.0367

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.103 AC: 454

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00966 AC: 1173

Asia WGS AF: 0.00895 AC: 32 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

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	0.12
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.75
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.14
Sift	Benign	0.60	T
Sift4G	Benign	0.63	T
Polyphen		0.012	B
Vest4		0.18
MVP		0.28
MPC		0.10
ClinPred		0.014	T
GERP RS		4.0
Varity_R		0.32
gMVP		0.54
Mutation Taster		=93/7	polymorphism (auto)

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: rs34397316; hg19: chr11-122722440;