rs1719976

chr18-5533189-G-Achr18-5533189-G-T

Variant summary

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

The NM_012307.5(EPB41L3):c.-12+10724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,020 control chromosomes in the GnomAD database, including 5,623 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 0.25 (5623 hom., cov: 32)
• Consequence: EPB41L3 NM_012307.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L3	NM_012307.5	c.-12+10724C>T		intron_variant		ENST00000341928.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L3	ENST00000341928.7	c.-12+10724C>T		intron_variant		1	NM_012307.5

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38263 AN: 151902 Hom.: 5614 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.252 AC: 38310 AN: 152020 Hom.: 5623 Cov.: 32 AF XY: 0.246 AC XY: 18290 AN XY: 74322

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.265

Alfa AF: 0.195 Hom.: 1859

Bravo AF: 0.268

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.72
Dann	Benign	0.42

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: rs1719976; hg19: chr18-5533188;