Genetic Variant EPB41L5:p.Thr8Thr (chr2-120019108-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020909.4(EPB41L5):c.24A>G(p.Thr8Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,610,300 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 6 hom. )

Consequence

EPB41L5
NM_020909.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.65

Publications

1 publications found

Variant links:

Genes affected

EPB41L5 (HGNC:19819): (erythrocyte membrane protein band 4.1 like 5) Predicted to enable cytoskeletal protein binding activity and protein domain specific binding activity. Predicted to be involved in actomyosin structure organization. Predicted to act upstream of or within several processes, including chordate embryonic development; embryonic foregut morphogenesis; and mesoderm morphogenesis. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EPB41L5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 2-120019108-A-G is Benign according to our data. Variant chr2-120019108-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651310.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L5	NM_020909.4 link	c.24A>G	p.Thr8Thr	synonymous_variant	Exon 2 of 25	ENST00000263713.10	NP_065960.2	Q9HCM4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L5	ENST00000263713.10 link	c.24A>G	p.Thr8Thr	synonymous_variant	Exon 2 of 25	1	NM_020909.4	ENSP00000263713.5		Q9HCM4-1

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

239

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00122

AC:

303

AN:

247928

AF XY:

0.00124

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.000420

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000927

Gnomad NFE exome

AF:

0.00223

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00230

AC:

3357

AN:

1458220

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

1666

AN XY:

725684

show subpopulations

African (AFR)

AF:

0.000483

AC:

AN:

33138

American (AMR)

AF:

0.000554

AC:

AN:

43354

Ashkenazi Jewish (ASJ)

AF:

0.000231

AC:

AN:

25954

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

85992

European-Finnish (FIN)

AF:

0.00116

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5268

European-Non Finnish (NFE)

AF:

0.00286

AC:

3177

AN:

1111274

Other (OTH)

AF:

0.00120

AC:

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

162

324

485

647

809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152080

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

100

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.000651

AC:

AN:

41478

American (AMR)

AF:

0.00151

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.000945

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00257

AC:

175

AN:

67988

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00194

Hom.:

Bravo

AF:

0.00151

EpiCase

AF:

0.00185

EpiControl

AF:

0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EPB41L5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.8

(source)

DANN

Benign

0.48

PhyloP100

-1.7

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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.

2-120019108-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over