rs7122442

Variant names:

• chr11-108607413-A-G
• rs7122442
• XM_017017397.2:c.35+70T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-108607413-A-G
• chr11-108607413-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017017397.2(EXPH5):​c.35+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,200 control chromosomes in the GnomAD database, including 2,424 homozygotes. 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: 𝑓 0.13 (2424 hom., cov: 32)
• Consequence: EXPH5 XM_017017397.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 4 publications found

Genes affected

EXPH5 (HGNC:30578): (exophilin 5) The protein encoded by this gene is a member of the synaptotagmin-like protein (Slp) family lacking a C2 domain. It contains an N-terminal synaptotagmin-like homology domain (SHD), and is a ras-related protein Rab-27B effector protein. This protein is thought to be involved in exosome secretion and intracellular vesicle trafficking. Reduced expression of this gene results in keratin filament defects. Mutations in this gene have been associated with some cases of epidermolysis bullosa, an inherited skin fragility disorder. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

EXPH5 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXPH5	XM_017017397.2	c.35+70T>C		intron_variant	Intron 1 of 6		XP_016872886.2
EXPH5	XM_017017398.2	c.35+70T>C		intron_variant	Intron 1 of 6		XP_016872887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19513 AN: 152082 Hom.: 2413 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 19555 AN: 152200 Hom.: 2424 Cov.: 32 AF XY: 0.125 AC XY: 9283 AN XY: 74430

African (AFR) AF: 0.325 AC: 13487 AN: 41484

American (AMR) AF: 0.0911 AC: 1393 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 270 AN: 3468

East Asian (EAS) AF: 0.0699 AC: 363 AN: 5190

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4826

European-Finnish (FIN) AF: 0.0442 AC: 469 AN: 10608

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0450 AC: 3058 AN: 68020

Other (OTH) AF: 0.119 AC: 252 AN: 2110

Alfa AF: 0.0781 Hom.: 180

Bravo AF: 0.141

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.58
PhyloP100		0.57

Splicing

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

Other links and lift over

dbSNP: rs7122442; hg19: chr11-108478140;