Genetic Variant CD6:p.Thr217Met (chr11-61008714-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2685 hom., cov: 34)

Exomes 𝑓: 0.21 ( 35785 hom. )

Consequence

CD6
NM_006725.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.764

Publications

26 publications found

Variant links:

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]

CD6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
CD6	NM_006725.5 link	c.650C>T	p.Thr217Met	missense_variant	Exon 4 of 13	ENST00000313421.11	NP_006716.3	P30203-1Q8N4Q7Q6AZ88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD6	ENST00000313421.11 link	c.650C>T	p.Thr217Met	missense_variant	Exon 4 of 13	1	NM_006725.5	ENSP00000323280.7		P30203-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24160

AN:

152160

Hom.:

2685

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.171

AC:

39518

AN:

230678

AF XY:

0.174

show subpopulations

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 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.:

AF XY:

0.209

AC XY:

151022

AN XY:

722760

show subpopulations

African (AFR)

AF:

0.0375

AC:

1252

AN:

33390

American (AMR)

AF:

0.118

AC:

5169

AN:

43936

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

11133

AN:

25968

East Asian (EAS)

AF:

0.0237

AC:

933

AN:

39446

South Asian (SAS)

AF:

0.0776

AC:

6628

AN:

85410

European-Finnish (FIN)

AF:

0.173

AC:

8915

AN:

51450

Middle Eastern (MID)

AF:

0.319

AC:

1835

AN:

5754

European-Non Finnish (NFE)

AF:

0.233

AC:

258473

AN:

1108774

Other (OTH)

AF:

0.210

AC:

12615

AN:

60028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

14289

28578

42866

57155

71444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.159

AC:

24145

AN:

152278

Hom.:

2685

Cov.:

AF XY:

0.155

AC XY:

11576

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0437

AC:

1815

AN:

41572

American (AMR)

AF:

0.154

AC:

2350

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

1479

AN:

3468

East Asian (EAS)

AF:

0.0224

AC:

116

AN:

5178

South Asian (SAS)

AF:

0.0718

AC:

347

AN:

4830

European-Finnish (FIN)

AF:

0.167

AC:

1772

AN:

10616

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15509

AN:

67992

Other (OTH)

AF:

0.203

AC:

428

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1021

2042

3062

4083

5104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.227

Hom.:

4854

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: no assertion criteria provided

LINK: link

Submissions by phenotype

CD6-related disorder

Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;.;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.11

T;T;T;T;T

MetaRNN

Benign

0.0050

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.66

N;.;.;N;N

PhyloP100

0.76

PrimateAI

Benign

0.38

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

GERP RS

0.67

PromoterAI

0.00010

Neutral

(source)

Varity_R

0.20

gMVP

0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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11-61008714-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over