11-61125134-A-G

Position:

• chr11-61125134-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014207.4(CD5):​c.1382A>G​(p.His461Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,613,890 control chromosomes in the GnomAD database, including 686,879 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.94 (67476 hom., cov: 32)
  • Exomes 𝑓: 0.92 (619403 hom.)
• Consequence: CD5 NM_014207.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.4202916E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD5	NM_014207.4	c.1382A>G	p.His461Arg	missense_variant	9/11	ENST00000347785.8	NP_055022.2
CD5	NM_001346456.2	c.1211A>G	p.His404Arg	missense_variant	9/11		NP_001333385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD5	ENST00000347785.8	c.1382A>G	p.His461Arg	missense_variant	9/11	1	NM_014207.4	ENSP00000342681	P1

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143142 AN: 152136 Hom.: 67420 Cov.: 32

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.933

GnomAD3 exomes AF: 0.937 AC: 235418 AN: 251230 Hom.: 110437 AF XY: 0.934 AC XY: 126871 AN XY: 135794

Gnomad AFR exome AF: 0.985

Gnomad AMR exome AF: 0.961

Gnomad ASJ exome AF: 0.901

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.950

Gnomad FIN exome AF: 0.931

Gnomad NFE exome AF: 0.914

Gnomad OTH exome AF: 0.926

GnomAD4 exome AF: 0.920 AC: 1345114 AN: 1461636 Hom.: 619403 Cov.: 48 AF XY: 0.921 AC XY: 669547 AN XY: 727120

Gnomad4 AFR exome AF: 0.986

Gnomad4 AMR exome AF: 0.958

Gnomad4 ASJ exome AF: 0.904

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.951

Gnomad4 FIN exome AF: 0.930

Gnomad4 NFE exome AF: 0.911

Gnomad4 OTH exome AF: 0.924

GnomAD4 genome AF: 0.941 AC: 143257 AN: 152254 Hom.: 67476 Cov.: 32 AF XY: 0.942 AC XY: 70118 AN XY: 74434

Gnomad4 AFR AF: 0.983

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.955

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.934

Alfa AF: 0.919 Hom.: 152787

Bravo AF: 0.943

TwinsUK AF: 0.907 AC: 3364

ALSPAC AF: 0.910 AC: 3509

ESP6500AA AF: 0.984 AC: 4334

ESP6500EA AF: 0.913 AC: 7846

ExAC AF: 0.938 AC: 113869

Asia WGS AF: 0.987 AC: 3433 AN: 3478

EpiCase AF: 0.911

EpiControl AF: 0.912

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.10
DANN	Benign	0.62
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.036	T
MetaRNN	Benign	7.4e-7	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.11	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.051
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.35
ClinPred		0.0049	T
GERP RS		-2.6
Varity_R		0.034
gMVP		0.10

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: rs637186; hg19: chr11-60892606;