dbSNP rs2874686: EPB41L3:c.2122-104G>A (chr18-5407840-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_012307.5(EPB41L3):c.2122-104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,000,310 control chromosomes in the GnomAD database, including 387,296 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 0.72 ( 46144 hom., cov: 34)

Exomes 𝑓: 0.89 ( 341152 hom. )

Consequence

EPB41L3
NM_012307.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.740

Publications

10 publications found

Variant links:

Genes affected

EPB41L3 (HGNC:3380): (erythrocyte membrane protein band 4.1 like 3) Predicted to enable cytoskeletal protein-membrane anchor activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in several processes, including nervous system development; paranodal junction maintenance; and protein localization to paranode region of axon. Located in cell-cell junction and plasma membrane. Biomarker of meningioma. [provided by Alliance of Genome Resources, Apr 2022]

EPB41L3 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012307.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EPB41L3	NM_012307.5	MANE Select	c.2122-104G>A	intron	N/A	NP_036439.2
EPB41L3	NM_001384685.1		c.2176-104G>A	intron	N/A	NP_001371614.1
EPB41L3	NM_001330557.2		c.1615-104G>A	intron	N/A	NP_001317486.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
EPB41L3	ENST00000341928.7	TSL:1 MANE Select	c.2122-104G>A	intron	N/A	ENSP00000343158.2
EPB41L3	ENST00000540638.6	TSL:1	c.1615-872G>A	intron	N/A	ENSP00000442091.2
EPB41L3	ENST00000866153.1		c.1615-104G>A	intron	N/A	ENSP00000536212.1

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109945

AN:

152092

Hom.:

46145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.851

Gnomad AMR

AF:

0.813

Gnomad ASJ

AF:

0.907

Gnomad EAS

AF:

0.916

Gnomad SAS

AF:

0.801

Gnomad FIN

AF:

0.939

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.760

GnomAD4 exome

AF:

0.890

AC:

754668

AN:

848100

Hom.:

341152

AF XY:

0.890

AC XY:

396165

AN XY:

445286

show subpopulations

African (AFR)

AF:

0.248

AC:

5055

AN:

20402

American (AMR)

AF:

0.844

AC:

33850

AN:

40112

Ashkenazi Jewish (ASJ)

AF:

0.902

AC:

19023

AN:

21096

East Asian (EAS)

AF:

0.909

AC:

33482

AN:

36836

South Asian (SAS)

AF:

0.808

AC:

56454

AN:

69910

European-Finnish (FIN)

AF:

0.945

AC:

49449

AN:

52352

Middle Eastern (MID)

AF:

0.824

AC:

3731

AN:

4528

European-Non Finnish (NFE)

AF:

0.923

AC:

519580

AN:

563026

Other (OTH)

AF:

0.855

AC:

34044

AN:

39838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

3563

7125

10688

14250

17813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7084

14168

21252

28336

35420

<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:

0.722

AC:

109952

AN:

152210

Hom.:

46144

Cov.:

AF XY:

0.726

AC XY:

54000

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.258

AC:

10693

AN:

41450

American (AMR)

AF:

0.814

AC:

12455

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

3149

AN:

3470

East Asian (EAS)

AF:

0.916

AC:

4751

AN:

5186

South Asian (SAS)

AF:

0.801

AC:

3867

AN:

4830

European-Finnish (FIN)

AF:

0.939

AC:

9965

AN:

10616

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.918

AC:

62451

AN:

68032

Other (OTH)

AF:

0.763

AC:

1613

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

942

1885

2827

3770

4712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.857

Hom.:

171851

Bravo

AF:

0.693

Asia WGS

AF:

0.803

AC:

2791

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.057

(source)

DANN

Benign

0.63

PhyloP100

-0.74

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over