Genetic Variant ENST00000347529.7:c.-8+14896G>A (chr1-28902106-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000347529.7(EPB41):c.-8+14896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 923,504 control chromosomes in the GnomAD database, including 4,352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1572 hom., cov: 32)

Exomes 𝑓: 0.081 ( 2780 hom. )

Consequence

EPB41
ENST00000347529.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.11

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

elliptocytosis 1
Inheritance: SD, AR, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary elliptocytosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EPB41 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
EPB41	NM_001166005.2 link	c.-8+14896G>A	intron_variant	Intron 1 of 20	NP_001159477.1	P11171-1Q1WWM3Q59F12
EPB41	NM_203343.3 link	c.-8+14896G>A	intron_variant	Intron 1 of 16	NP_976218.1	Q59F12
EPB41	NM_001376022.1 link	c.-618+14896G>A	intron_variant	Intron 1 of 20	NP_001362951.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
EPB41	ENST00000347529.7 link	c.-8+14896G>A	intron_variant	Intron 1 of 16	1	ENSP00000290100.6	P11171-5
EPB41	ENST00000373800.7 link	c.-698+14896G>A	intron_variant	Intron 1 of 18	1	ENSP00000362906.3	P11171-4
EPB41	ENST00000373798.5 link	c.-8+8269G>A	intron_variant	Intron 1 of 20	5	ENSP00000362904.1	P11171-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18607

AN:

152066

Hom.:

1570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0806

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.0677

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.0820

Gnomad OTH

AF:

0.121

GnomAD4 exome

AF:

0.0812

AC:

62663

AN:

771320

Hom.:

2780

AF XY:

0.0813

AC XY:

29070

AN XY:

357348

show subpopulations

African (AFR)

AF:

0.260

AC:

3745

AN:

14416

American (AMR)

AF:

0.0707

AC:

AN:

934

Ashkenazi Jewish (ASJ)

AF:

0.0913

AC:

435

AN:

4764

East Asian (EAS)

AF:

0.000905

AC:

AN:

3314

South Asian (SAS)

AF:

0.0207

AC:

312

AN:

15088

European-Finnish (FIN)

AF:

0.0480

AC:

AN:

250

Middle Eastern (MID)

AF:

0.112

AC:

169

AN:

1510

European-Non Finnish (NFE)

AF:

0.0791

AC:

55834

AN:

705874

Other (OTH)

AF:

0.0829

AC:

2087

AN:

25170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2604

5208

7812

10416

13020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.122

AC:

18624

AN:

152184

Hom.:

1572

Cov.:

AF XY:

0.118

AC XY:

8760

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.247

AC:

10244

AN:

41470

American (AMR)

AF:

0.0804

AC:

1231

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0971

AC:

337

AN:

3472

East Asian (EAS)

AF:

0.00154

AC:

AN:

5188

South Asian (SAS)

AF:

0.0214

AC:

103

AN:

4822

European-Finnish (FIN)

AF:

0.0677

AC:

717

AN:

10594

Middle Eastern (MID)

AF:

0.134

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0820

AC:

5579

AN:

68018

Other (OTH)

AF:

0.120

AC:

254

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

795

1590

2384

3179

3974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0934

Hom.:

300

Bravo

AF:

0.131

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.037

(source)

DANN

Benign

0.50

PhyloP100

-4.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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ENST00000347529.7:c.-8+14896G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over