rs6141600

Variant names:

• chr20-36124388-T-C
• rs6141600
• ENST00000373946.7:c.-15+10589T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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 (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L1	NM_001258329.1	c.-15+10589T>C		intron_variant	Intron 2 of 22		NP_001245258.1
EPB41L1	NM_001424407.1	c.-10+11908T>C		intron_variant	Intron 2 of 20		NP_001411336.1
EPB41L1	NM_001424406.1	c.-10+11908T>C		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.-15+10589T>C		intron_variant	Intron 2 of 22	1		ENSP00000363057.4
EPB41L1	ENST00000202028.9	c.-10+11908T>C		intron_variant	Intron 2 of 19	1		ENSP00000202028.5
EPB41L1	ENST00000441639.5	c.-10+11908T>C		intron_variant	Intron 2 of 19	5		ENSP00000399214.1

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

African (AFR) AF: 0.635 AC: 26333 AN: 41488

American (AMR) AF: 0.268 AC: 4094 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1088 AN: 3468

East Asian (EAS) AF: 0.237 AC: 1229 AN: 5176

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4820

European-Finnish (FIN) AF: 0.302 AC: 3193 AN: 10588

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18990 AN: 67990

Other (OTH) AF: 0.370 AC: 781 AN: 2112

Alfa AF: 0.308 Hom.: 23694

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
PhyloP100		-0.50
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: rs6141600; hg19: chr20-34712310;