rs1719976

Variant names:

• chr18-5533189-G-A
• rs1719976
• NM_012307.5:c.-12+10724C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-5533189-G-A
• chr18-5533189-G-T

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPB41L3	NM_012307.5	c.-12+10724C>T		intron_variant	Intron 1 of 22	ENST00000341928.7	NP_036439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L3	ENST00000341928.7	c.-12+10724C>T		intron_variant	Intron 1 of 22	1	NM_012307.5	ENSP00000343158.2

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

African (AFR) AF: 0.404 AC: 16744 AN: 41422

American (AMR) AF: 0.227 AC: 3477 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 935 AN: 3464

East Asian (EAS) AF: 0.152 AC: 788 AN: 5170

South Asian (SAS) AF: 0.206 AC: 994 AN: 4816

European-Finnish (FIN) AF: 0.128 AC: 1351 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13310 AN: 67958

Other (OTH) AF: 0.265 AC: 559 AN: 2110

Alfa AF: 0.197 Hom.: 2046

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
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1719976; hg19: chr18-5533188;