rs10499181

Variant names:

• chr6-131004380-T-C
• rs10499181
• NM_001431.4:c.-14-47881A>G

Variant summary

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

The NM_001431.4(EPB41L2):​c.-14-47881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 152,258 control chromosomes in the GnomAD database, including 238 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 0.025 (238 hom., cov: 32)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L2	NM_001431.4	c.-14-47881A>G		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.-14-47881A>G		intron_variant	Intron 1 of 19	1	NM_001431.4	ENSP00000338481.3

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3856 AN: 152140 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.00418

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00779

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0731

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0253 AC: 3849 AN: 152258 Hom.: 238 Cov.: 32 AF XY: 0.0291 AC XY: 2169 AN XY: 74444

African (AFR) AF: 0.00416 AC: 173 AN: 41558

American (AMR) AF: 0.00785 AC: 120 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3468

East Asian (EAS) AF: 0.277 AC: 1433 AN: 5166

South Asian (SAS) AF: 0.0324 AC: 156 AN: 4818

European-Finnish (FIN) AF: 0.0731 AC: 776 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0154 AC: 1048 AN: 68020

Other (OTH) AF: 0.0204 AC: 43 AN: 2112

Alfa AF: 0.0190 Hom.: 12

Bravo AF: 0.0213

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.85
PhyloP100		-0.30
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: rs10499181; hg19: chr6-131325520;