18-5560259-T-C

Variant summary

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

The XR_007066440.1(LOC107985145):n.357-236T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,142 control chromosomes in the GnomAD database, including 50,933 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 0.81 (50933 hom., cov: 32)
• Consequence: LOC107985145 XR_007066440.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

Genes affected

LOC107985145 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107985145	XR_007066440.1	n.357-236T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L3	ENST00000545076.5	c.-306+52081A>G		intron_variant		2
EPB41L3	ENST00000582592.1	c.55+17071A>G		intron_variant		5
EPB41L3	ENST00000637651.1	c.-306+70118A>G		intron_variant, NMD_transcript_variant		5
EPB41L3	ENST00000578431.1	n.324+70118A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122930 AN: 152024 Hom.: 50906 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.809 AC: 123013 AN: 152142 Hom.: 50933 Cov.: 32 AF XY: 0.809 AC XY: 60199 AN XY: 74378

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.810

Alfa AF: 0.889 Hom.: 76830

Bravo AF: 0.808

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	18
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1785394; hg19: chr18-5560258;