NM_006725.5:c.567T>C

Variant names:

• chr11-61008631-T-C
• rs61899223
• NM_006725.5:c.567T>C

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.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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.593
• Publications: 13 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]

ACMG classification

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.

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.567T>C	p.Thr189Thr	synonymous	Exon 4 of 13	NP_006716.3	P30203-1
	CD6	NM_001254750.2		c.567T>C	p.Thr189Thr	synonymous	Exon 4 of 11	NP_001241679.1	P30203-4
	CD6	NM_001254751.2		c.567T>C	p.Thr189Thr	synonymous	Exon 4 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.567T>C	p.Thr189Thr	synonymous	Exon 4 of 13	ENSP00000323280.7	P30203-1
	CD6	ENST00000352009.9	TSL:1	c.567T>C	p.Thr189Thr	synonymous	Exon 4 of 11	ENSP00000340628.5	P30203-4
	CD6	ENST00000452451.6	TSL:1	c.567T>C	p.Thr189Thr	synonymous	Exon 4 of 11	ENSP00000390676.2	P30203-5

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23873 AN: 152136 Hom.: 2143 Cov.: 33

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

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.: 31 AF XY: 0.135 AC XY: 97487 AN XY: 723400

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

GnomAD4 genome AF: 0.157 AC: 23904 AN: 152254 Hom.: 2147 Cov.: 33 AF XY: 0.153 AC XY: 11384 AN XY: 74450

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: 64 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8983 AN: 68004

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.147 Hom.: 1211

Bravo AF: 0.166

Asia WGS AF: 0.134 AC: 467 AN: 3478

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	-0.90
CADD	Benign	7.8
DANN	Benign	0.37
PhyloP100		-0.59
PromoterAI		-0.034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61899223; hg19: chr11-60776103; COSMIC: COSV57841690; COSMIC: COSV57841690;