18-5622072-A-T

Position:

• chr18-5622072-A-T

Variant summary

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

The NM_001384698.1(EPB41L3):​c.-306+8305T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,990 control chromosomes in the GnomAD database, including 2,925 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 0.20 (2925 hom., cov: 32)
• Consequence: EPB41L3 NM_001384698.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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]

EPB41L3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L3	NM_001384698.1	c.-306+8305T>A		intron_variant			NP_001371627.1
EPB41L3	NM_001384699.1	c.-306+8305T>A		intron_variant			NP_001371628.1
EPB41L3	NM_001384700.1	c.-306+8305T>A		intron_variant			NP_001371629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L3	ENST00000545076.5	c.-468+6850T>A		intron_variant		2		ENSP00000488626.1
EPB41L3	ENST00000578431.1	n.324+8305T>A		intron_variant		2
EPB41L3	ENST00000637651.1	n.-306+8305T>A		intron_variant		5		ENSP00000489681.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29680 AN: 151872 Hom.: 2922 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.195 AC: 29691 AN: 151990 Hom.: 2925 Cov.: 32 AF XY: 0.191 AC XY: 14159 AN XY: 74294

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.189

Alfa AF: 0.0856 Hom.: 115

Bravo AF: 0.195

Asia WGS AF: 0.125 AC: 431 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11874896; hg19: chr18-5622071;