rs6141600

chr20-36124388-T-C

Variant summary

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

The ENST00000373946.7(EPB41L1):c.-15+10589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,128 control chromosomes in the GnomAD database, including 12,786 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 0.38 (12786 hom., cov: 32)
• Consequence: EPB41L1 ENST00000373946.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

Genes affected

EPB41L1 (HGNC:3378): (erythrocyte membrane protein band 4.1 like 1) Erythrocyte membrane protein band 4.1 (EPB41) is a multifunctional protein that mediates interactions between the erythrocyte cytoskeleton and the overlying plasma membrane. The encoded protein binds and stabilizes D2 and D3 dopamine receptors at the neuronal plasma membrane. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L1	NM_001258329.1	c.-15+10589T>C		intron_variant
EPB41L1	NM_001258330.1	c.-21-1035T>C		intron_variant
EPB41L1	NM_001258331.2	c.-10+11908T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L1	ENST00000202028.9	c.-10+11908T>C		intron_variant		1
EPB41L1	ENST00000373946.7	c.-15+10589T>C		intron_variant		1		A1
EPB41L1	ENST00000373950.6	c.-10+2572T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57258 AN: 152010 Hom.: 12776 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.377 AC: 57300 AN: 152128 Hom.: 12786 Cov.: 32 AF XY: 0.372 AC XY: 27650 AN XY: 74368

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.370

Alfa AF: 0.291 Hom.: 8759

Bravo AF: 0.385

Asia WGS AF: 0.291 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.4
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6141600; hg19: chr20-34712310;