6-130871620-C-T

Variant names:

• chr6-130871620-C-T
• rs10499176
• NM_001431.4:c.2044-1494G>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.2044-1494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 152,296 control chromosomes in the GnomAD database, including 192 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 0.020 (192 hom., cov: 32)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L2	NM_001431.4	c.2044-1494G>A		intron_variant	Intron 14 of 19	ENST00000337057.8	NP_001422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8	c.2044-1494G>A		intron_variant	Intron 14 of 19	1	NM_001431.4	ENSP00000338481.3

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3025 AN: 152178 Hom.: 192 Cov.: 32

Gnomad AFR AF: 0.00401

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0198 AC: 3018 AN: 152296 Hom.: 192 Cov.: 32 AF XY: 0.0214 AC XY: 1594 AN XY: 74468

African (AFR) AF: 0.00399 AC: 166 AN: 41570

American (AMR) AF: 0.00771 AC: 118 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1341 AN: 5170

South Asian (SAS) AF: 0.0298 AC: 144 AN: 4828

European-Finnish (FIN) AF: 0.0156 AC: 166 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0142 AC: 963 AN: 68014

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0157 Hom.: 10

Bravo AF: 0.0201

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.52
PhyloP100		0.23
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: rs10499176; hg19: chr6-131192760;