20-36182312-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_012156.2(EPB41L1):c.531G>T(p.Pro177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,614,066 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: EPB41L1 NM_012156.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.05

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 20-36182312-G-T is Benign according to our data. Variant chr20-36182312-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 210950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-36182312-G-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BS2: High AC in GnomAd at 202 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L1	NM_012156.2	c.531G>T	p.Pro177=	synonymous_variant	6/22	ENST00000338074.7
LOC124904892	XR_007067571.1	n.265-664C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L1	ENST00000338074.7	c.531G>T	p.Pro177=	synonymous_variant	6/22	1	NM_012156.2	P5

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 202 AN: 152166 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00109 AC: 273 AN: 251448 Hom.: 0 AF XY: 0.00106 AC XY: 144 AN XY: 135902

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00213

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00150 AC: 2192 AN: 1461782 Hom.: 3 Cov.: 31 AF XY: 0.00145 AC XY: 1055 AN XY: 727192

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00187

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.00133 AC: 202 AN: 152284 Hom.: 1 Cov.: 32 AF XY: 0.000927 AC XY: 69 AN XY: 74464

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00232

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.00142

EpiCase AF: 0.00147

EpiControl AF: 0.00184

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2023	EPB41L1: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Apr 18, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 15, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	3.8
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs139137163; hg19: chr20-34770234;