18-5555974-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.316-2122T>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 0.617 in 152,018 control chromosomes in the GnomAD database, including 29,601 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 0.62 (29601 hom., cov: 32)
• Consequence: LOC107985145 XR_007066440.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107985145	XR_007066440.1	n.316-2122T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L3	ENST00000545076.5	c.-306+56366A>G		intron_variant		2
EPB41L3	ENST00000582592.1	c.55+21356A>G		intron_variant		5
EPB41L3	ENST00000637651.1	c.-305-66813A>G		intron_variant, NMD_transcript_variant		5
EPB41L3	ENST00000578431.1	n.325-66813A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93719 AN: 151900 Hom.: 29587 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.617 AC: 93774 AN: 152018 Hom.: 29601 Cov.: 32 AF XY: 0.616 AC XY: 45770 AN XY: 74292

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.579

Alfa AF: 0.634 Hom.: 5659

Bravo AF: 0.613

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.10
Dann	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1941001; hg19: chr18-5555973;