rs915171

Positions:

• chr6-130863774-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.2830-56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,240,628 control chromosomes in the GnomAD database, including 49,353 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 (7042 hom., cov: 32)
  • Exomes 𝑓: 0.27 (42311 hom.)
• Consequence: EPB41L2 NM_001431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L2	NM_001431.4	c.2830-56G>A		intron_variant		ENST00000337057.8	NP_001422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L2	ENST00000337057.8	c.2830-56G>A		intron_variant		1	NM_001431.4	ENSP00000338481	P2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45588 AN: 151962 Hom.: 7033 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.274 AC: 297964 AN: 1088548 Hom.: 42311 AF XY: 0.275 AC XY: 153399 AN XY: 557238

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.300 AC: 45626 AN: 152080 Hom.: 7042 Cov.: 32 AF XY: 0.300 AC XY: 22334 AN XY: 74326

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.283

Alfa AF: 0.276 Hom.: 6568

Bravo AF: 0.303

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.15
DANN	Benign	0.69

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: rs915171; hg19: chr6-131184914; COSMIC: COSV61354939;