11-61125763-C-T

Variant names:

• chr11-61125763-C-T
• rs2229177
• NM_014207.4:c.1412C>T

Variant summary

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

The NM_014207.4(CD5):​c.1412C>T​(p.Ala471Val) variant causes a missense change. The variant allele was found at a frequency of 0.539 in 1,606,602 control chromosomes in the GnomAD database, including 243,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24486 hom., cov: 31)
  • Exomes 𝑓: 0.54 (219297 hom.)
• Consequence: CD5 NM_014207.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.59
• Publications: 46 publications found

Genes affected

CD5 (HGNC:1685): (CD5 molecule) This gene encodes a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Members of this family are secreted or membrane-anchored proteins mainly found in cells associated with the immune system. This protein is a type-I transmembrane glycoprotein found on the surface of thymocytes, T lymphocytes and a subset of B lymphocytes. The encoded protein contains three SRCR domains and may act as a receptor to regulate T-cell proliferation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.2125587E-7).
• BP6: Variant 11-61125763-C-T is Benign according to our data. Variant chr11-61125763-C-T is described in ClinVar as Benign. ClinVar VariationId is 1268377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014207.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD5	NM_014207.4	MANE Select	c.1412C>T	p.Ala471Val	missense	Exon 10 of 11	NP_055022.2
	CD5	NM_001346456.2		c.1241C>T	p.Ala414Val	missense	Exon 10 of 11	NP_001333385.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD5	ENST00000347785.8	TSL:1 MANE Select	c.1412C>T	p.Ala471Val	missense	Exon 10 of 11	ENSP00000342681.3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84584 AN: 151822 Hom.: 24453 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.548

GnomAD2 exomes AF: 0.615 AC: 153298 AN: 249390 AF XY: 0.614

Gnomad AFR exome AF: 0.516

Gnomad AMR exome AF: 0.713

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.994

Gnomad FIN exome AF: 0.615

Gnomad NFE exome AF: 0.513

Gnomad OTH exome AF: 0.582

GnomAD4 exome AF: 0.537 AC: 781743 AN: 1454662 Hom.: 219297 Cov.: 31 AF XY: 0.543 AC XY: 393191 AN XY: 723762

African (AFR) AF: 0.515 AC: 17155 AN: 33328

American (AMR) AF: 0.704 AC: 31351 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 13979 AN: 25988

East Asian (EAS) AF: 0.996 AC: 39465 AN: 39622

South Asian (SAS) AF: 0.735 AC: 63092 AN: 85852

European-Finnish (FIN) AF: 0.608 AC: 32319 AN: 53176

Middle Eastern (MID) AF: 0.494 AC: 2841 AN: 5746

European-Non Finnish (NFE) AF: 0.496 AC: 548514 AN: 1106290

Other (OTH) AF: 0.549 AC: 33027 AN: 60144

GnomAD4 genome AF: 0.557 AC: 84663 AN: 151940 Hom.: 24486 Cov.: 31 AF XY: 0.567 AC XY: 42085 AN XY: 74266

African (AFR) AF: 0.514 AC: 21309 AN: 41422

American (AMR) AF: 0.632 AC: 9644 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1916 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5117 AN: 5164

South Asian (SAS) AF: 0.760 AC: 3665 AN: 4824

European-Finnish (FIN) AF: 0.628 AC: 6621 AN: 10548

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34645 AN: 67920

Other (OTH) AF: 0.554 AC: 1171 AN: 2114

Alfa AF: 0.532 Hom.: 48992

Bravo AF: 0.556

TwinsUK AF: 0.496 AC: 1841

ALSPAC AF: 0.490 AC: 1888

ESP6500AA AF: 0.530 AC: 2337

ESP6500EA AF: 0.503 AC: 4328

ExAC AF: 0.610 AC: 74012

Asia WGS AF: 0.848 AC: 2949 AN: 3478

EpiCase AF: 0.505

EpiControl AF: 0.513

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 25402503, 27169428)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.65	T
MetaRNN	Benign	8.2e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.6
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Benign	0.038	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.17
MPC		0.96
ClinPred		0.022	T
GERP RS		5.0
Varity_R		0.19
gMVP		0.21
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2229177; hg19: chr11-60893235; COSMIC: COSV106441847; COSMIC: COSV106441847;