dbSNP rs35423185: EPB41:c.1845+548C>T (chr1-29053860-C-T) – 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.1845+548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 153,630 control chromosomes in the GnomAD database, including 9,006 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 ( 8879 hom., cov: 32)

Exomes 𝑓: 0.37 ( 127 hom. )

Consequence

EPB41
NM_001376013.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.716

Publications

1 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41	NM_001376013.1 link	c.1845+548C>T		intron_variant	Intron 12 of 20	ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9 link	c.1845+548C>T		intron_variant	Intron 12 of 20	5	NM_001376013.1	ENSP00000345259.4

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46486

AN:

151882

Hom.:

8872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0951

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.0719

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.502

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.367

AC:

596

AN:

1626

Hom.:

127

Cov.:

AF XY:

0.367

AC XY:

338

AN XY:

922

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.322

AC:

AN:

286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0625

AC:

AN:

South Asian (SAS)

AF:

0.284

AC:

AN:

204

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.405

AC:

429

AN:

1060

Other (OTH)

AF:

0.318

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.306

AC:

46504

AN:

152004

Hom.:

8879

Cov.:

AF XY:

0.313

AC XY:

23243

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0949

AC:

3939

AN:

41486

American (AMR)

AF:

0.339

AC:

5175

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1359

AN:

3468

East Asian (EAS)

AF:

0.0721

AC:

373

AN:

5174

South Asian (SAS)

AF:

0.324

AC:

1563

AN:

4820

European-Finnish (FIN)

AF:

0.502

AC:

5280

AN:

10528

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27729

AN:

67936

Other (OTH)

AF:

0.312

AC:

659

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1487

2973

4460

5946

7433

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:

0.351

Hom.:

1371

Bravo

AF:

0.278

Asia WGS

AF:

0.210

AC:

730

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.5

(source)

DANN

Benign

0.65

PhyloP100

0.72

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over