20-36197999-C-A

Variant names:

• chr20-36197999-C-A
• rs112471399
• NM_012156.2:c.1626C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4 BP7 BS2

The NM_012156.2(EPB41L1):​c.1626C>A​(p.Pro542Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P542P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: EPB41L1 NM_012156.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.287).
• BP7: Synonymous conserved (PhyloP=-2.74 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L1	NM_012156.2	MANE Select	c.1626C>A	p.Pro542Pro	synonymous	Exon 14 of 22	NP_036288.2	Q9H4G0-1
	EPB41L1	NM_001433605.1		c.1626C>A	p.Pro542Pro	synonymous	Exon 14 of 23	NP_001420534.1
	EPB41L1	NM_001258329.1		c.1626C>A	p.Pro542Pro	synonymous	Exon 15 of 23	NP_001245258.1	A0A0C4DH22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L1	ENST00000338074.7	TSL:1 MANE Select	c.1626C>A	p.Pro542Pro	synonymous	Exon 14 of 22	ENSP00000337168.2	Q9H4G0-1
	EPB41L1	ENST00000373946.7	TSL:1	c.1626C>A	p.Pro542Pro	synonymous	Exon 15 of 23	ENSP00000363057.4	A0A0C4DH22
	EPB41L1	ENST00000202028.9	TSL:1	c.1404C>A	p.Pro468Pro	synonymous	Exon 13 of 20	ENSP00000202028.5	Q9H4G0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460984 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726816

African (AFR) AF: 0.0000598 AC: 2 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111446

Other (OTH) AF: 0.0000663 AC: 4 AN: 60352

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.025
DANN	Benign	0.56
PhyloP100		-2.7
PromoterAI		0.0099	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs112471399; hg19: chr20-34785921;