11-61008737-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006725.5(CD6):c.673C>T(p.Arg225Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,606,102 control chromosomes in the GnomAD database, including 93,780 homozygotes. In-silico tool predicts 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 0.38 (12084 hom., cov: 34)
  • Exomes 𝑓: 0.33 (81696 hom.)
• Consequence: CD6 NM_006725.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.938

Genes affected

CD6 (HGNC:1691): (CD6 molecule) This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.8583746E-4).
• BP6: Variant 11-61008737-C-T is Benign according to our data. Variant chr11-61008737-C-T is described in ClinVar as [Benign]. Clinvar id is 3060458.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD6	NM_006725.5	c.673C>T	p.Arg225Trp	missense_variant	4/13	ENST00000313421.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD6	ENST00000313421.11	c.673C>T	p.Arg225Trp	missense_variant	4/13	1	NM_006725.5	P2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57913 AN: 152078 Hom.: 12070 Cov.: 34

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.392

GnomAD3 exomes AF: 0.308 AC: 72739 AN: 235972 Hom.: 11964 AF XY: 0.307 AC XY: 39509 AN XY: 128896

Gnomad AFR exome AF: 0.559

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.232

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.330 AC: 479520 AN: 1453906 Hom.: 81696 Cov.: 59 AF XY: 0.327 AC XY: 236434 AN XY: 722380

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.381 AC: 57965 AN: 152196 Hom.: 12084 Cov.: 34 AF XY: 0.370 AC XY: 27528 AN XY: 74404

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.392

Alfa AF: 0.339 Hom.: 16910

Bravo AF: 0.398

TwinsUK AF: 0.341 AC: 1263

ALSPAC AF: 0.351 AC: 1352

ESP6500AA AF: 0.541 AC: 2381

ESP6500EA AF: 0.333 AC: 2855

ExAC AF: 0.305 AC: 36568

Asia WGS AF: 0.241 AC: 840 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CD6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T;.;.;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.77	T;T;T;T;T
MetaRNN	Benign	0.00049	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.075	N;.;.;N;N
MutationTaster	Benign	0.93	P;P;P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.9	D;D;D;D;D
REVEL	Benign	0.077
Sift	Benign	0.17	T;D;D;D;D
Sift4G	Benign	0.072	T;D;D;D;D
Polyphen		0.37	B;.;B;P;B
Vest4		0.088
MPC		1.4
ClinPred		0.024	T
GERP RS		1.2
Varity_R		0.51
gMVP		0.89

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: rs11230563; hg19: chr11-60776209; COSMIC: COSV57835912; COSMIC: COSV57835912;