rs1050922

Variant names:

• chr11-61017880-A-G
• rs1050922
• NM_006725.5:c.1704A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -5.40
• Publications: 29 publications found

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]

ENSG00000303405 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006725.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD6	NM_006725.5	MANE Select	c.1704A>G	p.Ser568Ser	synonymous	Exon 11 of 13	NP_006716.3	P30203-1
	CD6	NM_001254750.2		c.1608A>G	p.Ser536Ser	synonymous	Exon 10 of 11	NP_001241679.1	P30203-4
	CD6	NM_001254751.2		c.1581A>G	p.Ser527Ser	synonymous	Exon 10 of 11	NP_001241680.1	P30203-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD6	ENST00000313421.11	TSL:1 MANE Select	c.1704A>G	p.Ser568Ser	synonymous	Exon 11 of 13	ENSP00000323280.7	P30203-1
	CD6	ENST00000352009.9	TSL:1	c.1608A>G	p.Ser536Ser	synonymous	Exon 10 of 11	ENSP00000340628.5	P30203-4
	CD6	ENST00000452451.6	TSL:1	c.1581A>G	p.Ser527Ser	synonymous	Exon 10 of 11	ENSP00000390676.2	P30203-5

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92109 AN: 151728 Hom.: 29044 Cov.: 30

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

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.: 63 AF XY: 0.613 AC XY: 445818 AN XY: 727218

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

GnomAD4 genome AF: 0.607 AC: 92187 AN: 151846 Hom.: 29076 Cov.: 30 AF XY: 0.592 AC XY: 43905 AN XY: 74198

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

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CD6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.039
DANN	Benign	0.30
PhyloP100		-5.4
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs1050922; hg19: chr11-60785352; COSMIC: COSV57838914; COSMIC: COSV57838914;