15-43202924-G-T

Position:

• chr15-43202924-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001114134.2(EPB42):​c.1779+191C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 152,272 control chromosomes in the GnomAD database, including 376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.040 (376 hom., cov: 31)
• Consequence: EPB42 NM_001114134.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0210

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-43202924-G-T is Benign according to our data. Variant chr15-43202924-G-T is described in ClinVar as [Benign]. Clinvar id is 1231539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB42	NM_001114134.2	c.1779+191C>A		intron_variant		ENST00000441366.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB42	ENST00000441366.7	c.1779+191C>A		intron_variant		1	NM_001114134.2	P1
EPB42	ENST00000567019.2	n.1285+191C>A		intron_variant, non_coding_transcript_variant		1
EPB42	ENST00000540029.5	c.1545+191C>A		intron_variant		2
EPB42	ENST00000648595.1	c.1869+191C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6062 AN: 152154 Hom.: 374 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0399 AC: 6083 AN: 152272 Hom.: 376 Cov.: 31 AF XY: 0.0383 AC XY: 2852 AN XY: 74448

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0218 Hom.: 23

Bravo AF: 0.0455

Asia WGS AF: 0.0780 AC: 270 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.5
DANN	Benign	0.79

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: rs2271964; hg19: chr15-43495122;