Genetic Variant NM_006725.5:c.567T>C (chr11-61008631-T-C) – 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.567T>C(p.Thr189Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,607,596 control chromosomes in the GnomAD database, including 15,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2147 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13540 hom. )

Consequence

CD6
NM_006725.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.593

Publications

13 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.009).

BP6

Variant 11-61008631-T-C is Benign according to our data. Variant chr11-61008631-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059657.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.593 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD6	NM_006725.5 link	c.567T>C	p.Thr189Thr	synonymous_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.567T>C	p.Thr189Thr	synonymous_variant	Exon 4 of 13	1	NM_006725.5	ENSP00000323280.7		P30203-1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23873

AN:

152136

Hom.:

2143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0809

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0765

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.169

GnomAD2 exomes

AF:

0.131

AC:

30607

AN:

234100

AF XY:

0.134

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.0982

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.0803

Gnomad FIN exome

AF:

0.0792

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.133

AC:

193910

AN:

1455342

Hom.:

13540

Cov.:

AF XY:

0.135

AC XY:

97487

AN XY:

723400

show subpopulations

African (AFR)

AF:

0.252

AC:

8410

AN:

33404

American (AMR)

AF:

0.101

AC:

4426

AN:

43976

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

3813

AN:

25992

East Asian (EAS)

AF:

0.0665

AC:

2625

AN:

39472

South Asian (SAS)

AF:

0.160

AC:

13678

AN:

85240

European-Finnish (FIN)

AF:

0.0811

AC:

4213

AN:

51922

Middle Eastern (MID)

AF:

0.192

AC:

1106

AN:

5760

European-Non Finnish (NFE)

AF:

0.133

AC:

147282

AN:

1109428

Other (OTH)

AF:

0.139

AC:

8357

AN:

60148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

9537

19074

28610

38147

47684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5452

10904

16356

21808

27260

<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:

0.157

AC:

23904

AN:

152254

Hom.:

2147

Cov.:

AF XY:

0.153

AC XY:

11384

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.245

AC:

10167

AN:

41534

American (AMR)

AF:

0.111

AC:

1699

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

477

AN:

3472

East Asian (EAS)

AF:

0.0807

AC:

417

AN:

5166

South Asian (SAS)

AF:

0.150

AC:

723

AN:

4826

European-Finnish (FIN)

AF:

0.0765

AC:

813

AN:

10626

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8983

AN:

68004

Other (OTH)

AF:

0.169

AC:

358

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1098

2195

3293

4390

5488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.147

Hom.:

1211

Bravo

AF:

0.166

Asia WGS

AF:

0.134

AC:

467

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CD6-related disorder

Benign:1

Nov 01, 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

-0.90

CADD

Benign

7.8

(source)

DANN

Benign

0.37

PhyloP100

-0.59

PromoterAI

-0.034

Neutral

(source)

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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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