dbSNP rs2074225: CD6:p.Ala257Val (chr11-61008834-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.770C>T(p.Ala257Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,545,390 control chromosomes in the GnomAD database, including 258,994 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. A257A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.58 ( 25911 hom., cov: 34)

Exomes 𝑓: 0.57 ( 233083 hom. )

Consequence

CD6
NM_006725.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.50

Publications

40 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=2.1915762E-6).

BP6

Variant 11-61008834-C-T is Benign according to our data. Variant chr11-61008834-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059536.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD6	NM_006725.5 link	c.770C>T	p.Ala257Val	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.770C>T	p.Ala257Val	missense_variant	Exon 4 of 13	1	NM_006725.5	ENSP00000323280.7		P30203-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87928

AN:

152034

Hom.:

25897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.838

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.633

GnomAD2 exomes

AF:

0.535

AC:

103323

AN:

193210

AF XY:

0.541

show subpopulations

Gnomad AFR exome

AF:

0.641

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.737

Gnomad EAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.596

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.575

AC:

800477

AN:

1393238

Hom.:

233083

Cov.:

AF XY:

0.574

AC XY:

392418

AN XY:

683970

show subpopulations

African (AFR)

AF:

0.639

AC:

20329

AN:

31832

American (AMR)

AF:

0.407

AC:

15306

AN:

37590

Ashkenazi Jewish (ASJ)

AF:

0.736

AC:

16083

AN:

21854

East Asian (EAS)

AF:

0.426

AC:

16556

AN:

38870

South Asian (SAS)

AF:

0.471

AC:

35881

AN:

76110

European-Finnish (FIN)

AF:

0.442

AC:

21677

AN:

49064

Middle Eastern (MID)

AF:

0.752

AC:

4102

AN:

5458

European-Non Finnish (NFE)

AF:

0.593

AC:

637276

AN:

1074994

Other (OTH)

AF:

0.579

AC:

33267

AN:

57466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

16836

33673

50509

67346

84182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17856

35712

53568

71424

89280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.578

AC:

87977

AN:

152152

Hom.:

25911

Cov.:

AF XY:

0.568

AC XY:

42229

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.636

AC:

26415

AN:

41504

American (AMR)

AF:

0.498

AC:

7623

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.722

AC:

2507

AN:

3470

East Asian (EAS)

AF:

0.429

AC:

2217

AN:

5170

South Asian (SAS)

AF:

0.466

AC:

2249

AN:

4822

European-Finnish (FIN)

AF:

0.431

AC:

4563

AN:

10594

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40079

AN:

67974

Other (OTH)

AF:

0.635

AC:

1339

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1943

3886

5830

7773

9716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.592

Hom.:

13431

Bravo

AF:

0.592

TwinsUK

AF:

0.600

AC:

2224

ALSPAC

AF:

0.595

AC:

2292

ESP6500AA

AF:

0.549

AC:

2410

ESP6500EA

AF:

0.548

AC:

4699

ExAC

AF:

0.529

AC:

62295

Asia WGS

AF:

0.468

AC:

1628

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CD6-related disorder

Benign:1

Sep 24, 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

0.033

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.016

T;T;.;.;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.50

T;T;T;T;T

MetaRNN

Benign

0.0000022

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.5

N;.;.;N;N

PhyloP100

3.5

PrimateAI

Uncertain

0.66

PROVEAN

Benign

3.4

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;.;B;B;B

Vest4

0.083

MPC

0.96

ClinPred

0.00047

GERP RS

3.3

PromoterAI

0.028

Neutral

(source)

Varity_R

0.042

gMVP

0.46

Mutation Taster

=98/2

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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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