rs1162525540

Variant names:

• chr11-837480-C-T
• rs1162525540
• NM_004357.5:c.477C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-837480-C-T
• chr11-837480-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_004357.5(CD151):​c.477C>T​(p.Asn159Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CD151 NM_004357.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 2.07
• Publications: 0 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]

POLR2L (HGNC:9199): (RNA polymerase II, I and III subunit L) This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases. [provided by RefSeq, Jul 2008]

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=-0.46).
• BP6: Variant 11-837480-C-T is Benign according to our data. Variant chr11-837480-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1968518.
• BP7: Synonymous conserved (PhyloP=2.07 with no splicing effect.

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.477C>T	p.Asn159Asn	synonymous	Exon 7 of 9	NP_004348.2
	CD151	NM_001039490.2		c.477C>T	p.Asn159Asn	synonymous	Exon 6 of 8	NP_001034579.1	P48509
	CD151	NM_139029.2		c.477C>T	p.Asn159Asn	synonymous	Exon 7 of 9	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.477C>T	p.Asn159Asn	synonymous	Exon 7 of 9	ENSP00000380565.3	P48509
	CD151	ENST00000322008.9	TSL:1	c.477C>T	p.Asn159Asn	synonymous	Exon 7 of 9	ENSP00000324101.4	P48509
	CD151	ENST00000397421.5	TSL:1	c.477C>T	p.Asn159Asn	synonymous	Exon 6 of 8	ENSP00000380566.1	P48509

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249696 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460660 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726610

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Epidermolysis bullosa simplex 7, with nephropathy and deafness;C1867341:RAPH BLOOD GROUP SYSTEM (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1162525540; hg19: chr11-837480;