6-131011522-A-G

Position:

• chr6-131011522-A-G

Variant summary

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

The NM_001431.4(EPB41L2):​c.-15+51633T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,152 control chromosomes in the GnomAD database, including 7,359 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 0.30 (7359 hom., cov: 31)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L2	NM_001431.4	c.-15+51633T>C		intron_variant		ENST00000337057.8	NP_001422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8	c.-15+51633T>C		intron_variant		1	NM_001431.4	ENSP00000338481	P2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45183 AN: 152034 Hom.: 7339 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.297 AC: 45242 AN: 152152 Hom.: 7359 Cov.: 31 AF XY: 0.299 AC XY: 22250 AN XY: 74358

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.273

Alfa AF: 0.158 Hom.: 327

Bravo AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.78

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: rs6907809; hg19: chr6-131332662;