chr6-131034724-G-C

Variant names:

• chr6-131034724-G-C
• rs6908917
• NM_001431.4:c.-15+28431C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001431.4(EPB41L2):​c.-15+28431C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,086 control chromosomes in the GnomAD database, including 42,916 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 0.75 (42916 hom., cov: 31)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L2	NM_001431.4	c.-15+28431C>G		intron_variant	Intron 1 of 19	ENST00000337057.8	NP_001422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8	c.-15+28431C>G		intron_variant	Intron 1 of 19	1	NM_001431.4	ENSP00000338481.3

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113832 AN: 151968 Hom.: 42858 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.749 AC: 113949 AN: 152086 Hom.: 42916 Cov.: 31 AF XY: 0.749 AC XY: 55702 AN XY: 74342

African (AFR) AF: 0.776 AC: 32182 AN: 41458

American (AMR) AF: 0.717 AC: 10952 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2345 AN: 3470

East Asian (EAS) AF: 0.582 AC: 3002 AN: 5162

South Asian (SAS) AF: 0.743 AC: 3577 AN: 4814

European-Finnish (FIN) AF: 0.820 AC: 8686 AN: 10594

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50966 AN: 68006

Other (OTH) AF: 0.710 AC: 1495 AN: 2106

Alfa AF: 0.761 Hom.: 5468

Bravo AF: 0.740

Asia WGS AF: 0.667 AC: 2320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6908917; hg19: chr6-131355864;