dbSNP rs4897472: EPB41L2:c.1488-1532C>T (chr6-130891998-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001431.4(EPB41L2):c.1488-1532C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,026 control chromosomes in the GnomAD database, including 16,256 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 0.44 ( 16256 hom., cov: 32)

Consequence

EPB41L2
NM_001431.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.115

Variant links:

Genes affected

EPB41L2 (HGNC:3379): (erythrocyte membrane protein band 4.1 like 2) Predicted to enable PH domain binding activity; cytoskeletal protein binding activity; and structural molecule activity. Involved in positive regulation of protein localization to cell cortex. Located in cell junction; nucleoplasm; and plasma membrane. Colocalizes with COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

EPB41L2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L2	NM_001431.4 link	c.1488-1532C>T		intron_variant	Intron 10 of 19	ENST00000337057.8	NP_001422.1	O43491-1I6L9B1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8 link	c.1488-1532C>T		intron_variant	Intron 10 of 19	1	NM_001431.4	ENSP00000338481.3		O43491-1

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

67010

AN:

151908

Hom.:

16237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.655

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.420

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

GnomAD4 genome

AF:

0.441

AC:

67062

AN:

152026

Hom.:

16256

Cov.:

AF XY:

0.448

AC XY:

33327

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.456

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.515

Gnomad4 FIN

AF:

0.655

Gnomad4 NFE

AF:

0.518

Gnomad4 OTH

AF:

0.425

Alfa

AF:

0.336

Hom.:

1003

Bravo

AF:

0.416

Asia WGS

AF:

0.504

AC:

1751

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.3

DANN

Benign

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over