11-108509254-A-G

Position:

• chr11-108509254-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015065.3(EXPH5):​c.*283T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 272,844 control chromosomes in the GnomAD database, including 2,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1439 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1548 hom.)
• Consequence: EXPH5 NM_015065.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.242

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-108509254-A-G is Benign according to our data. Variant chr11-108509254-A-G is described in ClinVar as [Benign]. Clinvar id is 1242733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXPH5	NM_015065.3	c.*283T>C		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.*283T>C		3_prime_UTR_variant	6/6	1	NM_015065.3	ENSP00000265843	P4
EXPH5	ENST00000525344.5	c.*283T>C		3_prime_UTR_variant	7/7	1		ENSP00000432546	A2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19508 AN: 152106 Hom.: 1437 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.151 AC: 18172 AN: 120620 Hom.: 1548 Cov.: 2 AF XY: 0.152 AC XY: 9265 AN XY: 61050

Gnomad4 AFR exome AF: 0.0719

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.128 AC: 19518 AN: 152224 Hom.: 1439 Cov.: 32 AF XY: 0.132 AC XY: 9821 AN XY: 74432

Gnomad4 AFR AF: 0.0754

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.128

Alfa AF: 0.143 Hom.: 2154

Bravo AF: 0.121

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.97
DANN	Benign	0.63

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: rs3741060; hg19: chr11-108379981;