rs7238186

Positions:

• chr18-5479094-A-G

Variant summary

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

The NM_012307.5(EPB41L3):​c.184-656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,264 control chromosomes in the GnomAD database, including 4,087 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 0.22 (4087 hom., cov: 33)
• Consequence: EPB41L3 NM_012307.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L3	NM_012307.5	c.184-656T>C		intron_variant		ENST00000341928.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L3	ENST00000341928.7	c.184-656T>C		intron_variant		1	NM_012307.5
	ENST00000577527.1	n.378-532A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34234 AN: 152146 Hom.: 4088 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.225 AC: 34239 AN: 152264 Hom.: 4087 Cov.: 33 AF XY: 0.222 AC XY: 16494 AN XY: 74450

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.250

Alfa AF: 0.261 Hom.: 5294

Bravo AF: 0.221

Asia WGS AF: 0.181 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.9
DANN	Benign	0.70

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: rs7238186; hg19: chr18-5479093;