chr11-44618696-C-T

Variant names:

• chr11-44618696-C-T
• rs79095986
• NM_002231.4:c.699C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002231.4(CD82):​c.699C>T​(p.Gly233Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,613,228 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (34 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (39 hom.)
• Consequence: CD82 NM_002231.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.35
• Publications: 3 publications found

Genes affected

CD82 (HGNC:6210): (CD82 molecule) This metastasis suppressor gene product is a membrane glycoprotein that is a member of the transmembrane 4 superfamily. Expression of this gene has been shown to be downregulated in tumor progression of human cancers and can be activated by p53 through a consensus binding sequence in the promoter. Its expression and that of p53 are strongly correlated, and the loss of expression of these two proteins is associated with poor survival for prostate cancer patients. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 11-44618696-C-T is Benign according to our data. Variant chr11-44618696-C-T is described in ClinVar as Benign. ClinVar VariationId is 786594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.35 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0115 (1742/152092) while in subpopulation AFR AF = 0.038 (1579/41514). AF 95% confidence interval is 0.0365. There are 34 homozygotes in GnomAd4. There are 818 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002231.4. 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
	CD82	NM_002231.4	MANE Select	c.699C>T	p.Gly233Gly	synonymous	Exon 9 of 10	NP_002222.1	P27701-1
	CD82	NM_001024844.2		c.624C>T	p.Gly208Gly	synonymous	Exon 8 of 9	NP_001020015.1	P27701-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD82	ENST00000227155.9	TSL:1 MANE Select	c.699C>T	p.Gly233Gly	synonymous	Exon 9 of 10	ENSP00000227155.4	P27701-1
	CD82	ENST00000878578.1		c.840C>T	p.Gly280Gly	synonymous	Exon 9 of 10	ENSP00000548637.1
	CD82	ENST00000878563.1		c.699C>T	p.Gly233Gly	synonymous	Exon 9 of 10	ENSP00000548622.1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1736 AN: 151976 Hom.: 34 Cov.: 31

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00864

GnomAD2 exomes AF: 0.00290 AC: 728 AN: 250618 AF XY: 0.00224

Gnomad AFR exome AF: 0.0382

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.00123 AC: 1803 AN: 1461136 Hom.: 39 Cov.: 33 AF XY: 0.00109 AC XY: 789 AN XY: 726890

African (AFR) AF: 0.0418 AC: 1400 AN: 33468

American (AMR) AF: 0.00212 AC: 95 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39680

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52976

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5766

European-Non Finnish (NFE) AF: 0.0000971 AC: 108 AN: 1111774

Other (OTH) AF: 0.00263 AC: 159 AN: 60372

GnomAD4 genome AF: 0.0115 AC: 1742 AN: 152092 Hom.: 34 Cov.: 31 AF XY: 0.0110 AC XY: 818 AN XY: 74336

African (AFR) AF: 0.0380 AC: 1579 AN: 41514

American (AMR) AF: 0.00863 AC: 132 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000391 AC: 2 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67960

Other (OTH) AF: 0.00855 AC: 18 AN: 2106

Alfa AF: 0.00459 Hom.: 6

Bravo AF: 0.0130

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.7
DANN	Benign	0.47
PhyloP100		1.3
PromoterAI		-0.0046	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs79095986; hg19: chr11-44640246; COSMIC: COSV99907463; COSMIC: COSV99907463;