20-36175586-C-T

Variant names:

• chr20-36175586-C-T
• rs191128724
• NM_012156.2:c.213C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_012156.2(EPB41L1):​c.213C>T​(p.Ala71Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: EPB41L1 NM_012156.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.93
• Publications: 0 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

LOC124904892 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 20-36175586-C-T is Benign according to our data. Variant chr20-36175586-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2652288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.93 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 23 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.213C>T	p.Ala71Ala	synonymous	Exon 3 of 22	NP_036288.2	Q9H4G0-1
	EPB41L1	NM_001433605.1		c.213C>T	p.Ala71Ala	synonymous	Exon 3 of 23	NP_001420534.1
	EPB41L1	NM_001258329.1		c.213C>T	p.Ala71Ala	synonymous	Exon 4 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.213C>T	p.Ala71Ala	synonymous	Exon 3 of 22	ENSP00000337168.2	Q9H4G0-1
	EPB41L1	ENST00000373946.7	TSL:1	c.213C>T	p.Ala71Ala	synonymous	Exon 4 of 23	ENSP00000363057.4	A0A0C4DH22
	EPB41L1	ENST00000202028.9	TSL:1	c.27C>T	p.Ala9Ala	synonymous	Exon 3 of 20	ENSP00000202028.5	Q9H4G0-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251478 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.5
DANN	Benign	0.77
PhyloP100		-2.9

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: rs191128724; hg19: chr20-34763508;