11-836023-C-G

Variant names:

• chr11-836023-C-G
• rs28475448
• NM_004357.5:c.-7-40C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004357.5(CD151):​c.-7-40C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD151 NM_004357.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 14 publications found

Genes affected

CD151 (HGNC:1630): (CD151 molecule (Raph blood group)) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. It is involved in cellular processes including cell adhesion and may regulate integrin trafficking and/or function. This protein enhances cell motility, invasion and metastasis of cancer cells. Multiple alternatively spliced transcript variants that encode the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

CD151 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex 7, with nephropathy and deafness

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004357.5. 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
	CD151	NM_004357.5	MANE Select	c.-7-40C>G		intron	N/A	NP_004348.2
	CD151	NM_001039490.2		c.-7-40C>G		intron	N/A	NP_001034579.1	P48509
	CD151	NM_139029.2		c.-7-40C>G		intron	N/A	NP_620598.1	P48509

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD151	ENST00000397420.9	TSL:1 MANE Select	c.-7-40C>G		intron	N/A	ENSP00000380565.3	P48509
	CD151	ENST00000322008.9	TSL:1	c.-7-40C>G		intron	N/A	ENSP00000324101.4	P48509
	CD151	ENST00000397421.5	TSL:1	c.-7-40C>G		intron	N/A	ENSP00000380566.1	P48509

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000285 AC: 3 AN: 1053282 Hom.: 0 Cov.: 14 AF XY: 0.00000185 AC XY: 1 AN XY: 541474

African (AFR) AF: 0.00 AC: 0 AN: 25710

American (AMR) AF: 0.00 AC: 0 AN: 43430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23554

East Asian (EAS) AF: 0.00 AC: 0 AN: 37758

South Asian (SAS) AF: 0.00 AC: 0 AN: 77062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4912

European-Non Finnish (NFE) AF: 0.00000404 AC: 3 AN: 742206

Other (OTH) AF: 0.00 AC: 0 AN: 47110

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 8019

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.40
PhyloP100		-0.99
PromoterAI		0.0092	Neutral

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: rs28475448; hg19: chr11-836023;