15-43202091-ACT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001114134.2(EPB42):c.1780-116_1780-115del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,451,038 control chromosomes in the GnomAD database, including 873 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (386 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (487 hom.)
• Consequence: EPB42 NM_001114134.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.950

Genes affected

EPB42 (HGNC:3381): (erythrocyte membrane protein band 4.2) Erythrocyte membrane protein band 4.2 is an ATP-binding protein which may regulate the association of protein 3 with ankyrin. It probably has a role in erythrocyte shape and mechanical property regulation. Mutations in the EPB42 gene are associated with recessive spherocytic elliptocytosis and recessively transmitted hereditary hemolytic anemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-43202091-ACT-A is Benign according to our data. Variant chr15-43202091-ACT-A is described in ClinVar as [Benign]. Clinvar id is 1283031.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-43202091-ACT-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB42	NM_001114134.2	c.1780-116_1780-115del		intron_variant		ENST00000441366.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB42	ENST00000441366.7	c.1780-116_1780-115del		intron_variant		1	NM_001114134.2	P1
EPB42	ENST00000567019.2	n.1286-116_1286-115del		intron_variant, non_coding_transcript_variant		1
EPB42	ENST00000540029.5	c.1546-116_1546-115del		intron_variant		2
EPB42	ENST00000648595.1	c.1870-116_1870-115del		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6108 AN: 151896 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.00561

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000780

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.00756 AC: 9827 AN: 1299024 Hom.: 487 AF XY: 0.00708 AC XY: 4608 AN XY: 651300

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.00987

Gnomad4 ASJ exome AF: 0.00319

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.00443

Gnomad4 FIN exome AF: 0.0000201

Gnomad4 NFE exome AF: 0.000420

Gnomad4 OTH exome AF: 0.0178

GnomAD4 genome AF: 0.0403 AC: 6129 AN: 152014 Hom.: 386 Cov.: 32 AF XY: 0.0387 AC XY: 2876 AN XY: 74310

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.00582

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000780

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0221 Hom.: 23

Bravo AF: 0.0458

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

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: rs10564871; hg19: chr15-43494289;