Variant chr11-108509585-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015065.3(EXPH5):c.5922A>G(p.Thr1974=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,592,320 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 15 hom., cov: 32)

Exomes 𝑓: 0.016 ( 224 hom. )

Consequence

EXPH5
NM_015065.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.54

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 links:

LOC112267909 (HGNC:):

LOC112267909 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 11-108509585-T-C is Benign according to our data. Variant chr11-108509585-T-C is described in ClinVar as [Benign]. Clinvar id is 1285243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.54 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1787/152362) while in subpopulation NFE AF= 0.0182 (1238/68044). AF 95% confidence interval is 0.0174. There are 15 homozygotes in gnomad4. There are 862 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXPH5	NM_015065.3 linkuse as main transcript	c.5922A>G	p.Thr1974=	synonymous_variant	6/6	ENST00000265843.9	NP_055880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXPH5	ENST00000265843.9 linkuse as main transcript	c.5922A>G	p.Thr1974=	synonymous_variant	6/6	1	NM_015065.3	ENSP00000265843	P4	Q8NEV8-1
EXPH5	ENST00000525344.5 linkuse as main transcript	c.5901A>G	p.Thr1967=	synonymous_variant	7/7	1		ENSP00000432546	A2	Q8NEV8-2

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1787

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0244

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0138

AC:

3183

AN:

229922

Hom.:

AF XY:

0.0142

AC XY:

1756

AN XY:

123864

show subpopulations

Gnomad AFR exome

AF:

0.00376

Gnomad AMR exome

AF:

0.00539

Gnomad ASJ exome

AF:

0.00819

Gnomad EAS exome

AF:

0.0000573

Gnomad SAS exome

AF:

0.00420

Gnomad FIN exome

AF:

0.0249

Gnomad NFE exome

AF:

0.0206

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.0160

AC:

23064

AN:

1439958

Hom.:

224

Cov.:

AF XY:

0.0158

AC XY:

11322

AN XY:

715502

show subpopulations

Gnomad4 AFR exome

AF:

0.00312

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.00906

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00360

Gnomad4 FIN exome

AF:

0.0253

Gnomad4 NFE exome

AF:

0.0181

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0117

AC:

1787

AN:

152362

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

862

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00293

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0244

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.1

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over