Variant chr5-66054546-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001253697.2(ERBIN):c.3228A>G(p.Arg1076Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,614,024 control chromosomes in the GnomAD database, including 23,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2457 hom., cov: 32)

Exomes 𝑓: 0.15 ( 21408 hom. )

Consequence

ERBIN
NM_001253697.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.995

Variant links:

Genes affected

ERBIN (HGNC:15842): (erbb2 interacting protein) This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ERBIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 5-66054546-A-G is Benign according to our data. Variant chr5-66054546-A-G is described in ClinVar as [Benign]. Clinvar id is 1169279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.995 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERBIN	NM_001253697.2 linkuse as main transcript	c.3228A>G	p.Arg1076Arg	synonymous_variant	21/26	ENST00000284037.10	NP_001240626.1	Q96RT1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERBIN	ENST00000284037.10 linkuse as main transcript	c.3228A>G	p.Arg1076Arg	synonymous_variant	21/26	1	NM_001253697.2	ENSP00000284037.4		Q96RT1-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23704

AN:

152036

Hom.:

2445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0925

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.176

GnomAD3 exomes

AF:

0.207

AC:

51937

AN:

251386

Hom.:

7800

AF XY:

0.195

AC XY:

26550

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.436

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.480

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.151

AC:

220940

AN:

1461870

Hom.:

21408

Cov.:

AF XY:

0.151

AC XY:

109568

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0933

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.156

AC:

23736

AN:

152154

Hom.:

2457

Cov.:

AF XY:

0.161

AC XY:

12007

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0929

Gnomad4 AMR

AF:

0.298

Gnomad4 ASJ

AF:

0.258

Gnomad4 EAS

AF:

0.456

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.149

Hom.:

2596

Bravo

AF:

0.168

Asia WGS

AF:

0.252

AC:

873

AN:

3478

EpiCase

AF:

0.135

EpiControl

AF:

0.137

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.6

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over