chr11-108509396-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_015065.3(EXPH5):​c.*140_*141insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 706,684 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 11 hom., cov: 32)
Exomes 𝑓: 0.0060 ( 27 hom. )

Consequence

EXPH5
NM_015065.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.774
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 -10 ACMG points.

BP6
Variant 11-108509396-G-GA is Benign according to our data. Variant chr11-108509396-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 2499330.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00577 (875/151704) while in subpopulation NFE AF= 0.00607 (412/67862). AF 95% confidence interval is 0.00559. There are 11 homozygotes in gnomad4. There are 523 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EXPH5NM_015065.3 linkuse as main transcriptc.*140_*141insT 3_prime_UTR_variant 6/6 ENST00000265843.9 NP_055880.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EXPH5ENST00000265843.9 linkuse as main transcriptc.*140_*141insT 3_prime_UTR_variant 6/61 NM_015065.3 ENSP00000265843 P4Q8NEV8-1
EXPH5ENST00000525344.5 linkuse as main transcriptc.*140_*141insT 3_prime_UTR_variant 7/71 ENSP00000432546 A2Q8NEV8-2

Frequencies

GnomAD3 genomes
AF:
0.00577
AC:
875
AN:
151586
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000896
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000722
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0391
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00607
Gnomad OTH
AF:
0.00241
GnomAD4 exome
AF:
0.00603
AC:
3344
AN:
554980
Hom.:
27
Cov.:
8
AF XY:
0.00585
AC XY:
1680
AN XY:
287226
show subpopulations
Gnomad4 AFR exome
AF:
0.000746
Gnomad4 AMR exome
AF:
0.00155
Gnomad4 ASJ exome
AF:
0.000218
Gnomad4 EAS exome
AF:
0.000123
Gnomad4 SAS exome
AF:
0.000330
Gnomad4 FIN exome
AF:
0.0298
Gnomad4 NFE exome
AF:
0.00576
Gnomad4 OTH exome
AF:
0.00507
GnomAD4 genome
AF:
0.00577
AC:
875
AN:
151704
Hom.:
11
Cov.:
32
AF XY:
0.00706
AC XY:
523
AN XY:
74110
show subpopulations
Gnomad4 AFR
AF:
0.000894
Gnomad4 AMR
AF:
0.000721
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0391
Gnomad4 NFE
AF:
0.00607
Gnomad4 OTH
AF:
0.00238
Alfa
AF:
0.00502
Hom.:
1
Bravo
AF:
0.00302

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 23, 2021See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs201174655; hg19: chr11-108380123; API