chr11-122850068-A-C

Variant names:

• chr11-122850068-A-C
• rs35411582
• NM_019604.4:c.47A>C

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.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

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=0.002638787).
• 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

Sel.	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.: 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

GnomAD2 exomes AF: 0.00222 AC: 553 AN: 249384 AF XY: 0.00168

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.: 14 Cov.: 31 AF XY: 0.000661 AC XY: 476 AN XY: 720056

African (AFR) AF: 0.0275 AC: 914 AN: 33252

American (AMR) AF: 0.00131 AC: 58 AN: 44200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25880

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53180

Middle Eastern (MID) AF: 0.000622 AC: 3 AN: 4822

European-Non Finnish (NFE) AF: 0.0000317 AC: 35 AN: 1104338

Other (OTH) AF: 0.00149 AC: 89 AN: 59780

GnomAD4 genome AF: 0.00793 AC: 1208 AN: 152282 Hom.: 18 Cov.: 32 AF XY: 0.00773 AC XY: 576 AN XY: 74478

African (AFR) AF: 0.0279 AC: 1159 AN: 41560

American (AMR) AF: 0.00222 AC: 34 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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: 10624

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68002

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00352 Hom.: 15

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

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	0.074
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
PhyloP100		0.51
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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs35411582; hg19: chr11-122720776;