6-131005252-G-T

Variant names:

• chr6-131005252-G-T
• rs1412540
• NM_001431.4:c.-14-48753C>A

Variant summary

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

The NM_001431.4(EPB41L2):​c.-14-48753C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 151,880 control chromosomes in the GnomAD database, including 55,627 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 0.85 (55627 hom., cov: 29)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L2	NM_001431.4	c.-14-48753C>A		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.-14-48753C>A		intron_variant	Intron 1 of 19	1	NM_001431.4	ENSP00000338481.3

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129348 AN: 151762 Hom.: 55564 Cov.: 29

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.852 AC: 129467 AN: 151880 Hom.: 55627 Cov.: 29 AF XY: 0.856 AC XY: 63508 AN XY: 74186

African (AFR) AF: 0.934 AC: 38708 AN: 41448

American (AMR) AF: 0.847 AC: 12926 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2483 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5154 AN: 5162

South Asian (SAS) AF: 0.882 AC: 4243 AN: 4810

European-Finnish (FIN) AF: 0.882 AC: 9246 AN: 10484

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54170 AN: 67934

Other (OTH) AF: 0.799 AC: 1682 AN: 2106

Alfa AF: 0.839 Hom.: 8741

Bravo AF: 0.850

Asia WGS AF: 0.942 AC: 3275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-0.054
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: rs1412540; hg19: chr6-131326392;