Variant 11-61119441-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014207.4(CD5):c.671C>T(p.Pro224Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,613,996 control chromosomes in the GnomAD database, including 25,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3085 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22740 hom. )

Consequence

CD5
NM_014207.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.195

Variant links:

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]

CD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055482984).

BP6

Variant 11-61119441-C-T is Benign according to our data. Variant chr11-61119441-C-T is described in ClinVar as [Benign]. Clinvar id is 1226331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD5	NM_014207.4 link	c.671C>T	p.Pro224Leu	missense_variant	5/11	ENST00000347785.8	NP_055022.2	P06127
CD5	NM_001346456.2 link	c.500C>T	p.Pro167Leu	missense_variant	5/11		NP_001333385.1	P06127

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD5	ENST00000347785.8 link	c.671C>T	p.Pro224Leu	missense_variant	5/11	1	NM_014207.4	ENSP00000342681.3		P06127

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28626

AN:

152094

Hom.:

3075

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.0681

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0786

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.150

AC:

37603

AN:

251282

Hom.:

3286

AF XY:

0.151

AC XY:

20582

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.0978

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.0718

Gnomad SAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.0827

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.171

AC:

250280

AN:

1461784

Hom.:

22740

Cov.:

AF XY:

0.171

AC XY:

124087

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.287

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.0519

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.0883

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.188

AC:

28665

AN:

152212

Hom.:

3085

Cov.:

AF XY:

0.183

AC XY:

13586

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.143

Gnomad4 EAS

AF:

0.0684

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.0786

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.180

Hom.:

5744

Bravo

AF:

0.197

TwinsUK

AF:

0.181

AC:

671

ALSPAC

AF:

0.183

AC:

704

ESP6500AA

AF:

0.278

AC:

1223

ESP6500EA

AF:

0.175

AC:

1505

ExAC

AF:

0.154

AC:

18713

Asia WGS

AF:

0.139

AC:

481

AN:

3478

EpiCase

AF:

0.182

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 27169428) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.38

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.0

REVEL

Benign

0.031

Sift

Benign

0.052

Sift4G

Uncertain

0.010

Polyphen

0.013

Vest4

0.043

MPC

0.30

ClinPred

0.0034

GERP RS

1.3

Varity_R

0.036

gMVP

0.29

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over