Variant chr1-29112504-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001376013.1(EPB41):c.2496+56T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,423,546 control chromosomes in the GnomAD database, including 176,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15103 hom., cov: 30)

Exomes 𝑓: 0.50 ( 161763 hom. )

Consequence

EPB41
NM_001376013.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.299

Variant links:

Genes affected

EPB41 (HGNC:3377): (erythrocyte membrane protein band 4.1) The protein encoded by this gene, together with spectrin and actin, constitute the red cell membrane cytoskeletal network. This complex plays a critical role in erythrocyte shape and deformability. Mutations in this gene are associated with type 1 elliptocytosis (EL1). Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Oct 2009]

EPB41 links:

EPB41 (HGNC:):

EPB41 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-29112504-T-A is Benign according to our data. Variant chr1-29112504-T-A is described in ClinVar as [Benign]. Clinvar id is 1236795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-29112504-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41	NM_001376013.1 linkuse as main transcript	c.2496+56T>A		intron_variant		ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9 linkuse as main transcript	c.2496+56T>A		intron_variant		5	NM_001376013.1	ENSP00000345259.4		P11171-1

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63508

AN:

151674

Hom.:

15104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.506

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.409

GnomAD4 exome

AF:

0.499

AC:

635205

AN:

1271754

Hom.:

161763

AF XY:

0.501

AC XY:

322091

AN XY:

642386

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.532

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.469

Gnomad4 SAS exome

AF:

0.556

Gnomad4 FIN exome

AF:

0.611

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.474

GnomAD4 genome

AF:

0.418

AC:

63524

AN:

151792

Hom.:

15103

Cov.:

AF XY:

0.432

AC XY:

32038

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.506

Gnomad4 EAS

AF:

0.447

Gnomad4 SAS

AF:

0.559

Gnomad4 FIN

AF:

0.630

Gnomad4 NFE

AF:

0.493

Gnomad4 OTH

AF:

0.411

Alfa

AF:

0.331

Hom.:

1012

Bravo

AF:

0.391

Asia WGS

AF:

0.458

AC:

1593

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.9

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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