dbSNP rs1050922: CD6:p.Ser568Ser (chr11-61017880-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_006725.5(CD6):c.1704A>G(p.Ser568Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,613,662 control chromosomes in the GnomAD database, including 317,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.61 ( 29076 hom., cov: 30)

Exomes 𝑓: 0.62 ( 288340 hom. )

Consequence

CD6
NM_006725.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -5.40

Publications

29 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:

ENSG00000303405 (HGNC:):

ENSG00000303405 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 11-61017880-A-G is Benign according to our data. Variant chr11-61017880-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059454.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-5.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD6	NM_006725.5 link	c.1704A>G	p.Ser568Ser	synonymous_variant	Exon 11 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.1704A>G	p.Ser568Ser	synonymous_variant	Exon 11 of 13	1	NM_006725.5	ENSP00000323280.7		P30203-1

Frequencies

GnomAD3 genomes

AF:

0.607

AC:

92109

AN:

151728

Hom.:

29044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.876

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.656

Gnomad OTH

AF:

0.657

GnomAD2 exomes

AF:

0.544

AC:

136776

AN:

251444

AF XY:

0.549

show subpopulations

Gnomad AFR exome

AF:

0.653

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.665

Gnomad OTH exome

AF:

0.623

GnomAD4 exome

AF:

0.616

AC:

900834

AN:

1461816

Hom.:

288340

Cov.:

AF XY:

0.613

AC XY:

445818

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.655

AC:

21917

AN:

33480

American (AMR)

AF:

0.378

AC:

16898

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.801

AC:

20946

AN:

26136

East Asian (EAS)

AF:

0.154

AC:

6110

AN:

39700

South Asian (SAS)

AF:

0.408

AC:

35197

AN:

86258

European-Finnish (FIN)

AF:

0.497

AC:

26528

AN:

53390

Middle Eastern (MID)

AF:

0.818

AC:

4720

AN:

5768

European-Non Finnish (NFE)

AF:

0.658

AC:

731379

AN:

1111966

Other (OTH)

AF:

0.615

AC:

37139

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20823

41647

62470

83294

104117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18754

37508

56262

75016

93770

<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:

0.607

AC:

92187

AN:

151846

Hom.:

29076

Cov.:

AF XY:

0.592

AC XY:

43905

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.652

AC:

26971

AN:

41382

American (AMR)

AF:

0.504

AC:

7692

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

2735

AN:

3464

East Asian (EAS)

AF:

0.164

AC:

844

AN:

5146

South Asian (SAS)

AF:

0.381

AC:

1832

AN:

4810

European-Finnish (FIN)

AF:

0.487

AC:

5125

AN:

10534

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.656

AC:

44562

AN:

67926

Other (OTH)

AF:

0.655

AC:

1383

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1708

3416

5124

6832

8540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.648

Hom.:

137057

Bravo

AF:

0.615

Asia WGS

AF:

0.324

AC:

1128

AN:

3478

EpiCase

AF:

0.694

EpiControl

AF:

0.692

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

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.039

(source)

DANN

Benign

0.30

PhyloP100

-5.4

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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