rs7748468

Positions:

• chr6-130934909-C-T

Variant summary

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

The NM_001431.4(EPB41L2):​c.706-8200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 151,590 control chromosomes in the GnomAD database, including 49,398 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 0.80 (49398 hom., cov: 28)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890

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=-0.98).
• 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.706-8200G>A		intron_variant		ENST00000337057.8	NP_001422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8	c.706-8200G>A		intron_variant		1	NM_001431.4	ENSP00000338481	P2

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121347 AN: 151472 Hom.: 49334 Cov.: 28

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.801 AC: 121468 AN: 151590 Hom.: 49398 Cov.: 28 AF XY: 0.808 AC XY: 59790 AN XY: 74028

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.742

Alfa AF: 0.762 Hom.: 5557

Bravo AF: 0.802

Asia WGS AF: 0.924 AC: 3211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.90
DANN	Benign	0.53

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: rs7748468; hg19: chr6-131256049;