rs3924849

chr18-5432331-G-A

Variant summary

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

The NM_012307.5(EPB41L3):c.912+1138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,932 control chromosomes in the GnomAD database, including 28,297 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 0.57 (28297 hom., cov: 31)
• Consequence: EPB41L3 NM_012307.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L3	NM_012307.5	c.912+1138C>T		intron_variant		ENST00000341928.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L3	ENST00000341928.7	c.912+1138C>T		intron_variant		1	NM_012307.5

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86247 AN: 151814 Hom.: 28292 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.568 AC: 86258 AN: 151932 Hom.: 28297 Cov.: 31 AF XY: 0.567 AC XY: 42107 AN XY: 74266

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.576

Alfa AF: 0.606 Hom.: 5840

Bravo AF: 0.549

Asia WGS AF: 0.520 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.0050
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: rs3924849; hg19: chr18-5432330;