chr15-43197599-TG-T

Position:

• chr15-43197599-TG-T

Variant summary

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

The NM_001114134.2(EPB42):​c.1914-136del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,034,990 control chromosomes in the GnomAD database, including 166 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (78 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (88 hom.)
• Consequence: EPB42 NM_001114134.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.212

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 15-43197599-TG-T is Benign according to our data. Variant chr15-43197599-TG-T is described in ClinVar as [Benign]. Clinvar id is 1266210.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB42	NM_001114134.2	c.1914-136del		intron_variant		ENST00000441366.7	NP_001107606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB42	ENST00000441366.7	c.1914-136del		intron_variant		1	NM_001114134.2	ENSP00000396616	P1
EPB42	ENST00000567019.2	n.1420-136del		intron_variant, non_coding_transcript_variant		1
EPB42	ENST00000540029.5	c.1680-136del		intron_variant		2		ENSP00000444699
EPB42	ENST00000648595.1	c.2004-136del		intron_variant				ENSP00000497777

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2793 AN: 152156 Hom.: 78 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00366 AC: 3235 AN: 882716 Hom.: 88 AF XY: 0.00438 AC XY: 1973 AN XY: 450856

Gnomad4 AFR exome AF: 0.0589

Gnomad4 AMR exome AF: 0.00312

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000297

Gnomad4 SAS exome AF: 0.0260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.00550

GnomAD4 genome AF: 0.0183 AC: 2794 AN: 152274 Hom.: 78 Cov.: 32 AF XY: 0.0172 AC XY: 1284 AN XY: 74458

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.0155 Hom.: 6

Bravo AF: 0.0205

Asia WGS AF: 0.0190 AC: 67 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

Jun 20, 2021

- -

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: rs143838364; hg19: chr15-43489797;