Genetic Variant NM_006725.5:c.673C>T (chr11-61008737-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.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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.38 ( 12084 hom., cov: 34)

Exomes 𝑓: 0.33 ( 81696 hom. )

Consequence

CD6
NM_006725.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.938

Publications

113 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=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 VariationId is 3060458.Status of the report is no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
CD6	NM_006725.5 link	c.673C>T	p.Arg225Trp	missense_variant	Exon 4 of 13	ENST00000313421.11	NP_006716.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD6	ENST00000313421.11 link	c.673C>T	p.Arg225Trp	missense_variant	Exon 4 of 13	1	NM_006725.5	ENSP00000323280.7

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57913

AN:

152078

Hom.:

12070

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.308

AC:

72739

AN:

235972

AF XY:

0.307

show subpopulations

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 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.:

AF XY:

0.327

AC XY:

236434

AN XY:

722380

show subpopulations

African (AFR)

AF:

0.563

AC:

18767

AN:

33314

American (AMR)

AF:

0.269

AC:

11865

AN:

44054

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

7539

AN:

25952

East Asian (EAS)

AF:

0.182

AC:

7193

AN:

39466

South Asian (SAS)

AF:

0.233

AC:

19985

AN:

85630

European-Finnish (FIN)

AF:

0.247

AC:

12764

AN:

51768

Middle Eastern (MID)

AF:

0.400

AC:

2297

AN:

5746

European-Non Finnish (NFE)

AF:

0.342

AC:

379422

AN:

1107950

Other (OTH)

AF:

0.328

AC:

19688

AN:

60026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

18016

36033

54049

72066

90082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12164

24328

36492

48656

60820

<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:

0.381

AC:

57965

AN:

152196

Hom.:

12084

Cov.:

AF XY:

0.370

AC XY:

27528

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.551

AC:

22874

AN:

41514

American (AMR)

AF:

0.315

AC:

4824

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

952

AN:

3472

East Asian (EAS)

AF:

0.178

AC:

923

AN:

5174

South Asian (SAS)

AF:

0.218

AC:

1054

AN:

4826

European-Finnish (FIN)

AF:

0.242

AC:

2570

AN:

10608

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23291

AN:

67980

Other (OTH)

AF:

0.392

AC:

828

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1819

3638

5458

7277

9096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.351

Hom.:

40485

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: no assertion criteria provided

LINK: link

Submissions by phenotype

CD6-related disorder

Benign:1

Oct 17, 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

0.29

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T;.;.;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.77

T;T;T;T;T

MetaRNN

Benign

0.00049

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.075

N;.;.;N;N

PhyloP100

0.94

PrimateAI

Benign

0.43

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

GERP RS

1.2

PromoterAI

-0.010

Neutral

(source)

Varity_R

0.51

gMVP

0.89

Mutation Taster

=99/1

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