rs1474976

Positions:

• chr20-36144450-C-A
• chr20-36144450-C-G

Variant summary

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

The ENST00000373946.7(EPB41L1):​c.-14-29314C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 152,182 control chromosomes in the GnomAD database, including 65,914 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 0.93 (65914 hom., cov: 31)
• Consequence: EPB41L1 ENST00000373946.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65

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 (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L1	NM_001258329.1	c.-14-29314C>A		intron_variant			NP_001245258.1
EPB41L1	NM_001258330.1	c.84+18923C>A		intron_variant			NP_001245259.1
EPB41L1	NM_001258331.2	c.-9-31101C>A		intron_variant			NP_001245260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L1	ENST00000202028.9	c.-9-31101C>A		intron_variant		1		ENSP00000202028
EPB41L1	ENST00000373946.7	c.-14-29314C>A		intron_variant		1		ENSP00000363057	A1
EPB41L1	ENST00000373950.6	c.-10+22634C>A		intron_variant		5		ENSP00000363061

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141356 AN: 152064 Hom.: 65856 Cov.: 31

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.945

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

GnomAD4 genome AF: 0.930 AC: 141475 AN: 152182 Hom.: 65914 Cov.: 31 AF XY: 0.934 AC XY: 69460 AN XY: 74392

Gnomad4 AFR AF: 0.980

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.934

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.961

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.945

Alfa AF: 0.897 Hom.: 55888

Bravo AF: 0.926

Asia WGS AF: 0.982 AC: 3413 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	0.015
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1474976; hg19: chr20-34732372;