rs2241002

Positions:

• chr11-61119441-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (3085 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22740 hom.)
• Consequence: CD5 NM_014207.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.195

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

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	UniProt
CD5	NM_014207.4	c.671C>T	p.Pro224Leu	missense_variant	5/11	ENST00000347785.8
CD5	NM_001346456.2	c.500C>T	p.Pro167Leu	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD5	ENST00000347785.8	c.671C>T	p.Pro224Leu	missense_variant	5/11	1	NM_014207.4	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28626 AN: 152094 Hom.: 3075 Cov.: 32

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

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.: 34 AF XY: 0.171 AC XY: 124087 AN XY: 727204

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.: 32 AF XY: 0.183 AC XY: 13586 AN XY: 74422

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

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	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.69
DEOGEN2	Benign	0.38	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.031
Sift	Benign	0.052	T
Sift4G	Uncertain	0.010	D
Polyphen		0.013	B
Vest4		0.043
MPC		0.30
ClinPred		0.0034	T
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

Other links and lift over

dbSNP: rs2241002; hg19: chr11-60886913; COSMIC: COSV61718903; COSMIC: COSV61718903;