rs1811949

chr6-130978039-T-Cchr6-130978039-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.-14-21540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,056 control chromosomes in the GnomAD database, including 21,926 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 0.50 (21926 hom., cov: 32)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L2	NM_001431.4	c.-14-21540A>G		intron_variant		ENST00000337057.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L2	ENST00000337057.8	c.-14-21540A>G		intron_variant		1	NM_001431.4	P2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76268 AN: 151938 Hom.: 21878 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.502 AC: 76375 AN: 152056 Hom.: 21926 Cov.: 32 AF XY: 0.508 AC XY: 37728 AN XY: 74308

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.453

Alfa AF: 0.396 Hom.: 8685

Bravo AF: 0.517

Asia WGS AF: 0.740 AC: 2575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.49
Dann	Benign	0.72

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: rs1811949; hg19: chr6-131299179;