rs77396561

chr20-36190742-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_012156.2(EPB41L1):c.1245C>T(p.Pro415=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,614,218 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (4 hom.)
• Consequence: EPB41L1 NM_012156.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.190

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]

LOC124904892 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 20-36190742-C-T is Benign according to our data. Variant chr20-36190742-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 402830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 520 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L1	NM_012156.2	c.1245C>T	p.Pro415=	synonymous_variant	11/22	ENST00000338074.7
LOC124904892	XR_007067571.1	n.264+5940G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L1	ENST00000338074.7	c.1245C>T	p.Pro415=	synonymous_variant	11/22	1	NM_012156.2	P5

Frequencies

GnomAD3 genomes AF: 0.00342 AC: 520 AN: 152222 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00931

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00132 AC: 332 AN: 251300 Hom.: 0 AF XY: 0.00110 AC XY: 150 AN XY: 135826

Gnomad AFR exome AF: 0.00917

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000695

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.000879 AC: 1285 AN: 1461880 Hom.: 4 Cov.: 32 AF XY: 0.000851 AC XY: 619 AN XY: 727240

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.00241

Gnomad4 ASJ exome AF: 0.000995

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000508

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.00347 AC: 529 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74490

Gnomad4 AFR AF: 0.00952

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00194 Hom.: 1

Bravo AF: 0.00398

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	EPB41L1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent, not in splice site, 0.9% African chromosomes in ExAC -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	11
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs77396561; hg19: chr20-34778664;