rs2105250

Positions:

• chr6-130963042-T-A
• chr6-130963042-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001431.4(EPB41L2):​c.-14-6543A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,106 control chromosomes in the GnomAD database, including 47,259 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 0.78 (47259 hom., cov: 31)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L2	NM_001431.4	c.-14-6543A>T		intron_variant		ENST00000337057.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L2	ENST00000337057.8	c.-14-6543A>T		intron_variant		1	NM_001431.4	P2

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119141 AN: 151988 Hom.: 47205 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.784 AC: 119252 AN: 152106 Hom.: 47259 Cov.: 31 AF XY: 0.791 AC XY: 58788 AN XY: 74356

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.729

Alfa AF: 0.752 Hom.: 5381

Bravo AF: 0.781

Asia WGS AF: 0.929 AC: 3231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs2105250; hg19: chr6-131284182;