chr6-130983093-C-T

Variant names:

• chr6-130983093-C-T
• rs9321265
• NM_001431.4:c.-14-26594G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001431.4(EPB41L2):​c.-14-26594G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,130 control chromosomes in the GnomAD database, including 3,581 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 0.20 (3581 hom., cov: 32)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L2	NM_001431.4	c.-14-26594G>A		intron_variant	Intron 1 of 19	ENST00000337057.8	NP_001422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8	c.-14-26594G>A		intron_variant	Intron 1 of 19	1	NM_001431.4	ENSP00000338481.3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30858 AN: 152012 Hom.: 3569 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.203 AC: 30902 AN: 152130 Hom.: 3581 Cov.: 32 AF XY: 0.204 AC XY: 15203 AN XY: 74354

African (AFR) AF: 0.289 AC: 11979 AN: 41506

American (AMR) AF: 0.261 AC: 3993 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 560 AN: 3456

East Asian (EAS) AF: 0.204 AC: 1054 AN: 5174

South Asian (SAS) AF: 0.198 AC: 954 AN: 4818

European-Finnish (FIN) AF: 0.159 AC: 1677 AN: 10574

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10060 AN: 68004

Other (OTH) AF: 0.192 AC: 405 AN: 2114

Alfa AF: 0.165 Hom.: 9669

Bravo AF: 0.213

Asia WGS AF: 0.231 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.74
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9321265; hg19: chr6-131304233;