18-5560259-T-G

Variant names:

• chr18-5560259-T-G
• rs1785394
• NM_001384698.1:c.-306+70118A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001384698.1(EPB41L3):​c.-306+70118A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 152,180 control chromosomes in the GnomAD database, including 57 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 0.015 (57 hom., cov: 32)
• Consequence: EPB41L3 NM_001384698.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 4 publications found

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]

ENSG00000264000 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L3	NM_001384698.1	c.-306+70118A>C		intron_variant	Intron 1 of 21		NP_001371627.1
EPB41L3	NM_001384699.1	c.-306+70118A>C		intron_variant	Intron 1 of 20		NP_001371628.1
EPB41L3	NM_001384700.1	c.-306+70118A>C		intron_variant	Intron 1 of 21		NP_001371629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L3	ENST00000545076.5	c.-306+52081A>C		intron_variant	Intron 3 of 21	2		ENSP00000488626.1
EPB41L3	ENST00000582592.1	c.55+17071A>C		intron_variant	Intron 1 of 2	5		ENSP00000463707.1
EPB41L3	ENST00000578431.1	n.324+70118A>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2248 AN: 152062 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00718

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

GnomAD4 genome AF: 0.0148 AC: 2255 AN: 152180 Hom.: 57 Cov.: 32 AF XY: 0.0142 AC XY: 1055 AN XY: 74404

African (AFR) AF: 0.0525 AC: 2180 AN: 41494

American (AMR) AF: 0.00340 AC: 52 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00 Hom.: 96101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.83
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1785394; hg19: chr18-5560258;