rs3741060

Variant names:

• chr11-108509254-A-G
• rs3741060
• NM_015065.3:c.*283T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ENSG00000296559 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015065.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXPH5	NM_015065.3	MANE Select	c.*283T>C		3_prime_UTR	Exon 6 of 6	NP_055880.2	Q8NEV8-1
	EXPH5	NM_001441059.1		c.*283T>C		3_prime_UTR	Exon 6 of 6	NP_001427988.1
	EXPH5	NM_001308019.2		c.*283T>C		3_prime_UTR	Exon 7 of 7	NP_001294948.1	Q8NEV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXPH5	ENST00000265843.9	TSL:1 MANE Select	c.*283T>C		3_prime_UTR	Exon 6 of 6	ENSP00000265843.4	Q8NEV8-1
	EXPH5	ENST00000525344.5	TSL:1	c.*283T>C		3_prime_UTR	Exon 7 of 7	ENSP00000432546.1	Q8NEV8-2
	ENSG00000296559	ENST00000740313.1		n.325-6057A>G		intron	N/A

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

African (AFR) AF: 0.0719 AC: 299 AN: 4156

American (AMR) AF: 0.127 AC: 672 AN: 5312

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 794 AN: 4796

East Asian (EAS) AF: 0.255 AC: 2562 AN: 10028

South Asian (SAS) AF: 0.240 AC: 569 AN: 2368

European-Finnish (FIN) AF: 0.140 AC: 977 AN: 7002

Middle Eastern (MID) AF: 0.161 AC: 101 AN: 626

European-Non Finnish (NFE) AF: 0.142 AC: 11076 AN: 78202

Other (OTH) AF: 0.138 AC: 1122 AN: 8130

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

African (AFR) AF: 0.0754 AC: 3134 AN: 41550

American (AMR) AF: 0.133 AC: 2029 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3468

East Asian (EAS) AF: 0.162 AC: 840 AN: 5176

South Asian (SAS) AF: 0.240 AC: 1158 AN: 4820

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10606

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9910 AN: 68002

Other (OTH) AF: 0.128 AC: 271 AN: 2114

Alfa AF: 0.140 Hom.: 2615

Bravo AF: 0.121

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.97
DANN	Benign	0.63
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3741060; hg19: chr11-108379981;