Variant chr15-43203014-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001114134.2(EPB42):c.1779+101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,432,564 control chromosomes in the GnomAD database, including 1,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.060 ( 827 hom., cov: 31)

Exomes 𝑓: 0.0098 ( 829 hom. )

Consequence

EPB42
NM_001114134.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.362

Variant links:

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]

EPB42 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 15-43203014-T-C is Benign according to our data. Variant chr15-43203014-T-C is described in ClinVar as [Benign]. Clinvar id is 1262595.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-43203014-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB42	NM_001114134.2 linkuse as main transcript	c.1779+101A>G		intron_variant		ENST00000441366.7	NP_001107606.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
EPB42	ENST00000441366.7 linkuse as main transcript	c.1779+101A>G	intron_variant	1	NM_001114134.2	ENSP00000396616	P1	P16452-1
EPB42	ENST00000567019.2 linkuse as main transcript	n.1285+101A>G	intron_variant, non_coding_transcript_variant	1
EPB42	ENST00000540029.5 linkuse as main transcript	c.1545+101A>G	intron_variant	2		ENSP00000444699
EPB42	ENST00000648595.1 linkuse as main transcript	c.1869+101A>G	intron_variant			ENSP00000497777		P16452-2

Frequencies

GnomAD3 genomes

AF:

0.0597

AC:

9074

AN:

152078

Hom.:

822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.0435

GnomAD4 exome

AF:

0.00976

AC:

12492

AN:

1280368

Hom.:

829

AF XY:

0.00880

AC XY:

5690

AN XY:

646322

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.00456

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000492

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0598

AC:

9106

AN:

152196

Hom.:

827

Cov.:

AF XY:

0.0578

AC XY:

4298

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.0220

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0119

Hom.:

214

Bravo

AF:

0.0679

Asia WGS

AF:

0.0830

AC:

288

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.88

CADD

Benign

6.1

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over