rs181581015

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_015065.3(EXPH5):c.5605G>A(p.Gly1869Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000871 in 1,606,678 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 1 hom. )

Consequence

EXPH5
NM_015065.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.645

Publications

2 publications found

Variant links:

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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

EXPH5 links:

ENSG00000296559 (HGNC:):

ENSG00000296559 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076721013).

BP6

Variant 11-108509902-C-T is Benign according to our data. Variant chr11-108509902-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3091267.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000243 (37/152204) while in subpopulation AFR AF = 0.000698 (29/41526). AF 95% confidence interval is 0.000499. There are 0 homozygotes in GnomAd4. There are 16 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015065.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXPH5	NM_015065.3	MANE Select	c.5605G>A	p.Gly1869Arg	missense	Exon 6 of 6	NP_055880.2	Q8NEV8-1
EXPH5	NM_001441059.1		c.5602G>A	p.Gly1868Arg	missense	Exon 6 of 6	NP_001427988.1
EXPH5	NM_001308019.2		c.5584G>A	p.Gly1862Arg	missense	Exon 7 of 7	NP_001294948.1	Q8NEV8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXPH5	ENST00000265843.9	TSL:1 MANE Select	c.5605G>A	p.Gly1869Arg	missense	Exon 6 of 6	ENSP00000265843.4	Q8NEV8-1
EXPH5	ENST00000525344.5	TSL:1	c.5584G>A	p.Gly1862Arg	missense	Exon 7 of 7	ENSP00000432546.1	Q8NEV8-2
ENSG00000296559	ENST00000740313.1		n.325-5409C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000111

AC:

AN:

244058

AF XY:

0.0000985

show subpopulations

Gnomad AFR exome

AF:

0.000682

Gnomad AMR exome

AF:

0.0000604

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000539

Gnomad OTH exome

AF:

0.000340

GnomAD4 exome

AF:

0.0000708

AC:

103

AN:

1454474

Hom.:

Cov.:

AF XY:

0.0000830

AC XY:

AN XY:

723322

show subpopulations

African (AFR)

AF:

0.000696

AC:

AN:

33026

American (AMR)

AF:

0.0000927

AC:

AN:

43168

Ashkenazi Jewish (ASJ)

AF:

0.0000390

AC:

AN:

25660

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39642

South Asian (SAS)

AF:

0.000260

AC:

AN:

84596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53248

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.0000370

AC:

AN:

1109400

Other (OTH)

AF:

0.000150

AC:

AN:

60028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000243

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41526

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.068

(source)

DANN

Benign

0.17

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0032

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0077

MetaSVM

Benign

-0.92

PhyloP100

0.65

PrimateAI

Benign

0.25

PROVEAN

Benign

2.5

REVEL

Benign

0.032

Sift

Benign

1.0

Sift4G

Benign

0.79

Vest4

0.053

MutPred

0.19

Loss of ubiquitination at K1871 (P = 0.0224)

MVP

0.040

MPC

0.041

ClinPred

0.0031

GERP RS

-0.87

gMVP

0.061

Mutation Taster

=96/4

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over