rs11230562

chr11-61008714-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.650C>T(p.Thr217Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,606,434 control chromosomes in the GnomAD database, including 38,470 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.16 (2685 hom., cov: 34)
  • Exomes 𝑓: 0.21 (35785 hom.)
• Consequence: CD6 NM_006725.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.764

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=0.005012661).
• BP6: Variant 11-61008714-C-T is Benign according to our data. Variant chr11-61008714-C-T is described in ClinVar as [Benign]. Clinvar id is 3056065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD6	NM_006725.5	c.650C>T	p.Thr217Met	missense_variant	4/13	ENST00000313421.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD6	ENST00000313421.11	c.650C>T	p.Thr217Met	missense_variant	4/13	1	NM_006725.5	P2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24160 AN: 152160 Hom.: 2685 Cov.: 34

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.171 AC: 39518 AN: 230678 Hom.: 4445 AF XY: 0.174 AC XY: 21892 AN XY: 125964

Gnomad AFR exome AF: 0.0430

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.0248

Gnomad SAS exome AF: 0.0746

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.211 AC: 306953 AN: 1454156 Hom.: 35785 Cov.: 46 AF XY: 0.209 AC XY: 151022 AN XY: 722760

Gnomad4 AFR exome AF: 0.0375

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.0237

Gnomad4 SAS exome AF: 0.0776

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.159 AC: 24145 AN: 152278 Hom.: 2685 Cov.: 34 AF XY: 0.155 AC XY: 11576 AN XY: 74460

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.203

Alfa AF: 0.230 Hom.: 3938

Bravo AF: 0.156

TwinsUK AF: 0.242 AC: 899

ALSPAC AF: 0.229 AC: 883

ESP6500AA AF: 0.0542 AC: 238

ESP6500EA AF: 0.238 AC: 2045

ExAC AF: 0.161 AC: 19349

Asia WGS AF: 0.0540 AC: 189 AN: 3478

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 22, 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	0.14
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T;.;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.11	T;T;T;T;T
MetaRNN	Benign	0.0050	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	N;.;.;N;N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	N;N;D;N;N
REVEL	Benign	0.046
Sift	Uncertain	0.0040	D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0	D;.;P;D;D
Vest4		0.075
MPC		2.0
ClinPred		0.012	T
GERP RS		0.67
Varity_R		0.20
gMVP		0.68

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: rs11230562; hg19: chr11-60776186; COSMIC: COSV57836892; COSMIC: COSV57836892;