11-108509396-G-GA

Position:

• chr11-108509396-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.774

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]

LOC112267909 (HGNC:):

ACMG classification

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
EXPH5	NM_015065.3	c.*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
EXPH5	ENST00000265843.9	c.*140_*141insT		3_prime_UTR_variant	6/6	1	NM_015065.3	ENSP00000265843	P4
EXPH5	ENST00000525344.5	c.*140_*141insT		3_prime_UTR_variant	7/7	1		ENSP00000432546	A2

Frequencies

GnomAD3 genomes AF: 0.00577 AC: 875 AN: 151586 Hom.: 11 Cov.: 32

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

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

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

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 23, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs201174655; hg19: chr11-108380123;