11-108570087-T-C

Variant names:

• chr11-108570087-T-C
• rs2852199
• NM_015065.3:c.119+23331A>G

Variant summary

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

The NM_015065.3(EXPH5):​c.119+23331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,076 control chromosomes in the GnomAD database, including 44,658 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 0.76 (44658 hom., cov: 32)
• Consequence: EXPH5 NM_015065.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXPH5	NM_015065.3	c.119+23331A>G		intron_variant	Intron 1 of 5	ENST00000265843.9	NP_055880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXPH5	ENST00000265843.9	c.119+23331A>G		intron_variant	Intron 1 of 5	1	NM_015065.3	ENSP00000265843.4
EXPH5	ENST00000525344.5	c.98+23331A>G		intron_variant	Intron 2 of 6	1		ENSP00000432546.1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116239 AN: 151958 Hom.: 44635 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.765 AC: 116310 AN: 152076 Hom.: 44658 Cov.: 32 AF XY: 0.767 AC XY: 57040 AN XY: 74334

African (AFR) AF: 0.715 AC: 29666 AN: 41484

American (AMR) AF: 0.754 AC: 11523 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2473 AN: 3472

East Asian (EAS) AF: 0.684 AC: 3522 AN: 5150

South Asian (SAS) AF: 0.795 AC: 3825 AN: 4814

European-Finnish (FIN) AF: 0.853 AC: 9029 AN: 10584

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53800 AN: 67962

Other (OTH) AF: 0.738 AC: 1560 AN: 2114

Alfa AF: 0.776 Hom.: 187435

Bravo AF: 0.753

Asia WGS AF: 0.793 AC: 2758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs2852199; hg19: chr11-108440814;