rs2874686

chr18-5407840-C-T

Variant summary

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

The NM_012307.5(EPB41L3):c.2122-104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,000,310 control chromosomes in the GnomAD database, including 387,296 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 0.72 (46144 hom., cov: 34)
  • Exomes 𝑓: 0.89 (341152 hom.)
• Consequence: EPB41L3 NM_012307.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740

Genes affected

EPB41L3 (HGNC:3380): (erythrocyte membrane protein band 4.1 like 3) Predicted to enable cytoskeletal protein-membrane anchor activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in several processes, including nervous system development; paranodal junction maintenance; and protein localization to paranode region of axon. Located in cell-cell junction and plasma membrane. Biomarker of meningioma. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L3	NM_012307.5	c.2122-104G>A		intron_variant		ENST00000341928.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L3	ENST00000341928.7	c.2122-104G>A		intron_variant		1	NM_012307.5

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109945 AN: 152092 Hom.: 46145 Cov.: 34

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.760

GnomAD4 exome AF: 0.890 AC: 754668 AN: 848100 Hom.: 341152 AF XY: 0.890 AC XY: 396165 AN XY: 445286

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.844

Gnomad4 ASJ exome AF: 0.902

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.945

Gnomad4 NFE exome AF: 0.923

Gnomad4 OTH exome AF: 0.855

GnomAD4 genome AF: 0.722 AC: 109952 AN: 152210 Hom.: 46144 Cov.: 34 AF XY: 0.726 AC XY: 54000 AN XY: 74416

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.918

Gnomad4 OTH AF: 0.763

Alfa AF: 0.896 Hom.: 115787

Bravo AF: 0.693

Asia WGS AF: 0.803 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.057
Dann	Benign	0.63

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: rs2874686; hg19: chr18-5407839;