11-60988884-G-T

Variant names:

• chr11-60988884-G-T
• rs12288280
• NM_006725.5:c.49+16970G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006725.5(CD6):​c.49+16970G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,140 control chromosomes in the GnomAD database, including 4,750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (4750 hom., cov: 33)
• Consequence: CD6 NM_006725.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 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.49+16970G>T		intron	N/A	NP_006716.3	P30203-1
	CD6	NM_001254750.2		c.49+16970G>T		intron	N/A	NP_001241679.1	P30203-4
	CD6	NM_001254751.2		c.49+16970G>T		intron	N/A	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.49+16970G>T		intron	N/A	ENSP00000323280.7	P30203-1
	CD6	ENST00000352009.9	TSL:1	c.49+16970G>T		intron	N/A	ENSP00000340628.5	P30203-4
	CD6	ENST00000452451.6	TSL:1	c.49+16970G>T		intron	N/A	ENSP00000390676.2	P30203-5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28935 AN: 152022 Hom.: 4729 Cov.: 33

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0887

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0875

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 28993 AN: 152140 Hom.: 4750 Cov.: 33 AF XY: 0.185 AC XY: 13781 AN XY: 74378

African (AFR) AF: 0.447 AC: 18535 AN: 41434

American (AMR) AF: 0.151 AC: 2304 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3472

East Asian (EAS) AF: 0.0880 AC: 456 AN: 5184

South Asian (SAS) AF: 0.0665 AC: 321 AN: 4824

European-Finnish (FIN) AF: 0.0484 AC: 514 AN: 10610

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0875 AC: 5952 AN: 67998

Other (OTH) AF: 0.195 AC: 411 AN: 2112

Alfa AF: 0.0684 Hom.: 155

Bravo AF: 0.210

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.80
PhyloP100		-0.44
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: rs12288280; hg19: chr11-60756356;