chr11-44619066-G-C

Variant names:

• chr11-44619066-G-C
• rs74885383
• NM_002231.4:c.744G>C

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.744G>C​(p.Leu248Leu) 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 1,613,774 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 0.012 (43 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (30 hom.)
• Consequence: CD82 NM_002231.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26
• Publications: 4 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=-0.63).
• BP6: Variant 11-44619066-G-C is Benign according to our data. Variant chr11-44619066-G-C is described in ClinVar as Benign. ClinVar VariationId is 789795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.26 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0118 (1801/152088) while in subpopulation AFR AF = 0.0416 (1725/41460). AF 95% confidence interval is 0.04. There are 43 homozygotes in GnomAd4. There are 864 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 43 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.744G>C	p.Leu248Leu	synonymous	Exon 10 of 10	NP_002222.1	P27701-1
	CD82	NM_001024844.2		c.669G>C	p.Leu223Leu	synonymous	Exon 9 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.744G>C	p.Leu248Leu	synonymous	Exon 10 of 10	ENSP00000227155.4	P27701-1
	CD82	ENST00000878578.1		c.885G>C	p.Leu295Leu	synonymous	Exon 10 of 10	ENSP00000548637.1
	CD82	ENST00000878563.1		c.744G>C	p.Leu248Leu	synonymous	Exon 10 of 10	ENSP00000548622.1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1801 AN: 151970 Hom.: 43 Cov.: 31

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00296 AC: 743 AN: 251286 AF XY: 0.00227

Gnomad AFR exome AF: 0.0405

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.00120 AC: 1747 AN: 1461686 Hom.: 30 Cov.: 32 AF XY: 0.00105 AC XY: 764 AN XY: 727166

African (AFR) AF: 0.0415 AC: 1390 AN: 33466

American (AMR) AF: 0.00170 AC: 76 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.000111 AC: 123 AN: 1111962

Other (OTH) AF: 0.00245 AC: 148 AN: 60394

GnomAD4 genome AF: 0.0118 AC: 1801 AN: 152088 Hom.: 43 Cov.: 31 AF XY: 0.0116 AC XY: 864 AN XY: 74346

African (AFR) AF: 0.0416 AC: 1725 AN: 41460

American (AMR) AF: 0.00281 AC: 43 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67992

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00386 Hom.: 3

Bravo AF: 0.0133

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

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	-0.63
CADD	Benign	7.5
DANN	Benign	0.65
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs74885383; hg19: chr11-44640616;