rs1474976

Variant names:

• chr20-36144450-C-A
• rs1474976
• ENST00000373946.7:c.-14-29314C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

EPB41L1 Gene-Disease associations (from GenCC):

• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• intellectual disability, autosomal dominant 11

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPB41L1	NM_001258329.1	c.-14-29314C>A		intron_variant	Intron 2 of 22		NP_001245258.1
EPB41L1	NM_001424407.1	c.-9-31101C>A		intron_variant	Intron 2 of 20		NP_001411336.1
EPB41L1	NM_001424406.1	c.-9-31101C>A		intron_variant	Intron 2 of 20		NP_001411335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L1	ENST00000373946.7	c.-14-29314C>A		intron_variant	Intron 2 of 22	1		ENSP00000363057.4
EPB41L1	ENST00000202028.9	c.-9-31101C>A		intron_variant	Intron 2 of 19	1		ENSP00000202028.5
EPB41L1	ENST00000441639.5	c.-9-31101C>A		intron_variant	Intron 2 of 19	5		ENSP00000399214.1

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

African (AFR) AF: 0.980 AC: 40689 AN: 41522

American (AMR) AF: 0.913 AC: 13964 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3242 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5169 AN: 5176

South Asian (SAS) AF: 0.961 AC: 4630 AN: 4820

European-Finnish (FIN) AF: 0.956 AC: 10137 AN: 10600

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60629 AN: 67988

Other (OTH) AF: 0.945 AC: 1998 AN: 2114

Alfa AF: 0.898 Hom.: 68781

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
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1474976; hg19: chr20-34732372;