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GeneBe

11-108509882-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_015065.3(EXPH5):c.5625G>A(p.Arg1875=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,609,088 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 32 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 26 hom. )

Consequence

EXPH5
NM_015065.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.238
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-108509882-C-T is Benign according to our data. Variant chr11-108509882-C-T is described in ClinVar as [Benign]. Clinvar id is 785381.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.238 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1673/152248) while in subpopulation AFR AF= 0.0381 (1582/41524). AF 95% confidence interval is 0.0365. There are 32 homozygotes in gnomad4. There are 780 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 32 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EXPH5NM_015065.3 linkuse as main transcriptc.5625G>A p.Arg1875= synonymous_variant 6/6 ENST00000265843.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EXPH5ENST00000265843.9 linkuse as main transcriptc.5625G>A p.Arg1875= synonymous_variant 6/61 NM_015065.3 P4Q8NEV8-1
EXPH5ENST00000525344.5 linkuse as main transcriptc.5604G>A p.Arg1868= synonymous_variant 7/71 A2Q8NEV8-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1669
AN:
152130
Hom.:
32
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0381
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00465
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00573
GnomAD3 exomes
AF:
0.00310
AC:
761
AN:
245786
Hom.:
15
AF XY:
0.00216
AC XY:
287
AN XY:
132836
show subpopulations
Gnomad AFR exome
AF:
0.0423
Gnomad AMR exome
AF:
0.00179
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000103
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000536
Gnomad OTH exome
AF:
0.00152
GnomAD4 exome
AF:
0.00110
AC:
1596
AN:
1456840
Hom.:
26
Cov.:
33
AF XY:
0.000923
AC XY:
669
AN XY:
724528
show subpopulations
Gnomad4 AFR exome
AF:
0.0390
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000141
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.00296
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1673
AN:
152248
Hom.:
32
Cov.:
32
AF XY:
0.0105
AC XY:
780
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0381
Gnomad4 AMR
AF:
0.00464
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00567
Alfa
AF:
0.00590
Hom.:
5
Bravo
AF:
0.0130
Asia WGS
AF:
0.00346
AC:
12
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 15, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
3.6
Dann
Benign
0.40

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

LitVar

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

Other links and lift over

dbSNP: rs115867994; hg19: chr11-108380609; API