rs9388860

Positions:

• chr6-130852312-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.*5+5819G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,162 control chromosomes in the GnomAD database, including 1,208 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 0.11 (1208 hom., cov: 32)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L2	NM_001431.4	c.*5+5819G>A		intron_variant		ENST00000337057.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L2	ENST00000337057.8	c.*5+5819G>A		intron_variant		1	NM_001431.4	P2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16923 AN: 152044 Hom.: 1203 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.111 AC: 16928 AN: 152162 Hom.: 1208 Cov.: 32 AF XY: 0.112 AC XY: 8346 AN XY: 74386

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.0828

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.109

Alfa AF: 0.126 Hom.: 247

Bravo AF: 0.0985

Asia WGS AF: 0.140 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.38

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: rs9388860; hg19: chr6-131173452;