6-130912868-A-G

Position:

• chr6-130912868-A-G

Variant summary

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

The NM_001431.4(EPB41L2):​c.811-4005T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,028 control chromosomes in the GnomAD database, including 46,907 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 (46907 hom., cov: 30)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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	Protein	UniProt
EPB41L2	NM_001431.4	c.811-4005T>C		intron_variant		ENST00000337057.8	NP_001422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8	c.811-4005T>C		intron_variant		1	NM_001431.4	ENSP00000338481.3

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118665 AN: 151910 Hom.: 46853 Cov.: 30

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.781 AC: 118777 AN: 152028 Hom.: 46907 Cov.: 30 AF XY: 0.788 AC XY: 58523 AN XY: 74296

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.724

Alfa AF: 0.718 Hom.: 53502

Bravo AF: 0.779

Asia WGS AF: 0.922 AC: 3205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.73

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: rs1334689; hg19: chr6-131234008;