Genetic Variant EPB41:c.1637-741C>A (chr1-29052363-C-A) – 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.1637-741C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,134 control chromosomes in the GnomAD database, including 8,875 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 0.31 ( 8875 hom., cov: 32)

Consequence

EPB41
NM_001376013.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.663

Publications

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

EPB41 links:

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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=-0.52).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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.1637-741C>A	intron	N/A	NP_001362942.1	P11171-1
EPB41	NM_001166005.2		c.1637-741C>A	intron	N/A	NP_001159477.1	P11171-1
EPB41	NM_001376014.1		c.1637-741C>A	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.1637-741C>A	intron	N/A	ENSP00000345259.4	P11171-1
EPB41	ENST00000349460.9	TSL:1	c.1637-741C>A	intron	N/A	ENSP00000317597.8	A0A2U3TZH6
EPB41	ENST00000347529.7	TSL:1	c.1532-741C>A	intron	N/A	ENSP00000290100.6	P11171-5

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46426

AN:

152016

Hom.:

8869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0949

Gnomad AMI

AF:

0.369

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.0642

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.306

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

GnomAD4 genome

AF:

0.305

AC:

46442

AN:

152134

Hom.:

8875

Cov.:

AF XY:

0.312

AC XY:

23207

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0948

AC:

3937

AN:

41544

American (AMR)

AF:

0.339

AC:

5175

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1360

AN:

3470

East Asian (EAS)

AF:

0.0643

AC:

334

AN:

5192

South Asian (SAS)

AF:

0.323

AC:

1555

AN:

4818

European-Finnish (FIN)

AF:

0.500

AC:

5276

AN:

10550

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27727

AN:

67974

Other (OTH)

AF:

0.310

AC:

653

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1495

2989

4484

5978

7473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.352

Hom.:

1396

Bravo

AF:

0.278

Asia WGS

AF:

0.204

AC:

710

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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