dbSNP rs203278: EPB41:c.-8+917T>C (chr1-28915685-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001376013.1(EPB41):c.-8+917T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 148,302 control chromosomes in the GnomAD database, including 17,577 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 0.46 ( 17577 hom., cov: 24)

Consequence

EPB41
NM_001376013.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.569

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: AD, SD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
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=-0.61).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376013.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPB41	NM_001376013.1	MANE Select	c.-8+917T>C	intron	N/A	NP_001362942.1	P11171-1
EPB41	NM_001166005.2		c.-8+28475T>C	intron	N/A	NP_001159477.1	P11171-1
EPB41	NM_001376014.1		c.-8+917T>C	intron	N/A	NP_001362943.1	A0A2U3TZH6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPB41	ENST00000343067.9	TSL:5 MANE Select	c.-8+917T>C	intron	N/A	ENSP00000345259.4	P11171-1
EPB41	ENST00000349460.9	TSL:1	c.-8+917T>C	intron	N/A	ENSP00000317597.8	A0A2U3TZH6
EPB41	ENST00000347529.7	TSL:1	c.-8+28475T>C	intron	N/A	ENSP00000290100.6	P11171-5

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

67530

AN:

148190

Hom.:

17562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.454

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

GnomAD4 genome

AF:

0.456

AC:

67586

AN:

148302

Hom.:

17577

Cov.:

AF XY:

0.458

AC XY:

32993

AN XY:

72066

show subpopulations

African (AFR)

AF:

0.664

AC:

26427

AN:

39782

American (AMR)

AF:

0.479

AC:

7033

AN:

14676

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1219

AN:

3452

East Asian (EAS)

AF:

0.849

AC:

4267

AN:

5028

South Asian (SAS)

AF:

0.541

AC:

2530

AN:

4674

European-Finnish (FIN)

AF:

0.309

AC:

3012

AN:

9754

Middle Eastern (MID)

AF:

0.455

AC:

132

AN:

290

European-Non Finnish (NFE)

AF:

0.322

AC:

21815

AN:

67658

Other (OTH)

AF:

0.453

AC:

945

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1539

3079

4618

6158

7697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.338

Hom.:

1589

Bravo

AF:

0.485

Asia WGS

AF:

0.695

AC:

2419

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

-0.57

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over