18-5432331-G-A

Variant names:

• chr18-5432331-G-A
• rs3924849
• NM_012307.5:c.912+1138C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000341928.7(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 ENST00000341928.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341928.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L3	NM_012307.5	MANE Select	c.912+1138C>T		intron	N/A	NP_036439.2
	EPB41L3	NM_001384685.1		c.912+1138C>T		intron	N/A	NP_001371614.1
	EPB41L3	NM_001330557.2		c.912+1138C>T		intron	N/A	NP_001317486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L3	ENST00000341928.7	TSL:1 MANE Select	c.912+1138C>T		intron	N/A	ENSP00000343158.2
	EPB41L3	ENST00000540638.6	TSL:1	c.912+1138C>T		intron	N/A	ENSP00000442091.2
	EPB41L3	ENST00000400111.8	TSL:5	c.487-3866C>T		intron	N/A	ENSP00000382981.5

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

African (AFR) AF: 0.221 AC: 9151 AN: 41388

American (AMR) AF: 0.656 AC: 10018 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2402 AN: 3470

East Asian (EAS) AF: 0.522 AC: 2687 AN: 5152

South Asian (SAS) AF: 0.568 AC: 2739 AN: 4818

European-Finnish (FIN) AF: 0.713 AC: 7541 AN: 10570

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.730 AC: 49572 AN: 67942

Other (OTH) AF: 0.576 AC: 1218 AN: 2116

Alfa AF: 0.612 Hom.: 11201

Bravo AF: 0.549

Asia WGS AF: 0.520 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0050
DANN	Benign	0.63
PhyloP100		-2.4
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: rs3924849; hg19: chr18-5432330;