11-836172-GCCCCCACCCCCA-GCCCCCACCCCCACCCCCA

Variant names:

• chr11-836172-G-GCCCCCA
• rs34987505
• NM_004357.5:c.84+36_84+41dupCACCCC

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_004357.5(CD151):​c.84+36_84+41dupCACCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00982 in 151,598 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (3 hom., cov: 34)
  • Exomes 𝑓: 0.0081 (77 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD151 NM_004357.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0680
• 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]

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: Benign. The variant received -12 ACMG points.

• BP6: Variant 11-836172-G-GCCCCCA is Benign according to our data. Variant chr11-836172-G-GCCCCCA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1556161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR,Unknown gene

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.84+36_84+41dupCACCCC		intron	N/A	NP_004348.2
	CD151	NM_001039490.2		c.84+36_84+41dupCACCCC		intron	N/A	NP_001034579.1	P48509
	CD151	NM_139029.2		c.84+36_84+41dupCACCCC		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.84+36_84+41dupCACCCC		intron	N/A	ENSP00000380565.3	P48509
	CD151	ENST00000322008.9	TSL:1	c.84+36_84+41dupCACCCC		intron	N/A	ENSP00000324101.4	P48509
	CD151	ENST00000397421.5	TSL:1	c.84+36_84+41dupCACCCC		intron	N/A	ENSP00000380566.1	P48509

Frequencies

GnomAD3 genomes AF: 0.00983 AC: 1489 AN: 151482 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.00245

Gnomad AMI AF: 0.0435

Gnomad AMR AF: 0.00539

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.00434

GnomAD2 exomes AF: 0.00556 AC: 1350 AN: 242670 AF XY: 0.00521

Gnomad AFR exome AF: 0.000973

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.000508

Gnomad EAS exome AF: 0.0000551

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.00771

Gnomad OTH exome AF: 0.00688

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00806 AC: 11248 AN: 1395380 Hom.: 77 Cov.: 25 AF XY: 0.00806 AC XY: 5616 AN XY: 696890

African (AFR) AF: 0.00182 AC: 59 AN: 32448

American (AMR) AF: 0.00398 AC: 177 AN: 44458

Ashkenazi Jewish (ASJ) AF: 0.000582 AC: 15 AN: 25754

East Asian (EAS) AF: 0.0000509 AC: 2 AN: 39306

South Asian (SAS) AF: 0.000495 AC: 42 AN: 84832

European-Finnish (FIN) AF: 0.0198 AC: 1020 AN: 51594

Middle Eastern (MID) AF: 0.000920 AC: 5 AN: 5432

European-Non Finnish (NFE) AF: 0.00901 AC: 9491 AN: 1053348

Other (OTH) AF: 0.00751 AC: 437 AN: 58208

GnomAD4 genome AF: 0.00982 AC: 1489 AN: 151598 Hom.: 3 Cov.: 34 AF XY: 0.00961 AC XY: 712 AN XY: 74088

African (AFR) AF: 0.00244 AC: 101 AN: 41416

American (AMR) AF: 0.00538 AC: 82 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4812

European-Finnish (FIN) AF: 0.0210 AC: 219 AN: 10412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0152 AC: 1033 AN: 67786

Other (OTH) AF: 0.00430 AC: 9 AN: 2094

Alfa AF: 0.00514 Hom.: 3

ClinVar

ClinVar submissions

Significance: Benign/Likely 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
PhyloP100		-0.068
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34987505; hg19: chr11-836172;