Genetic Variant ERBIN:p.Arg1076Arg (chr5-66054546-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

21 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253697.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ERBIN	NM_001253697.2	MANE Select	c.3228A>G	p.Arg1076Arg	synonymous	Exon 21 of 26	NP_001240626.1
ERBIN	NM_001253699.2		c.3228A>G	p.Arg1076Arg	synonymous	Exon 21 of 26	NP_001240628.1
ERBIN	NM_018695.4		c.3228A>G	p.Arg1076Arg	synonymous	Exon 21 of 25	NP_061165.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ERBIN	ENST00000284037.10	TSL:1 MANE Select	c.3228A>G	p.Arg1076Arg	synonymous	Exon 21 of 26	ENSP00000284037.4
ERBIN	ENST00000506030.6	TSL:1	c.3228A>G	p.Arg1076Arg	synonymous	Exon 21 of 26	ENSP00000426632.1
ERBIN	ENST00000380943.6	TSL:1	c.3228A>G	p.Arg1076Arg	synonymous	Exon 21 of 25	ENSP00000370330.2

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

GnomAD2 exomes

AF:

0.207

AC:

51937

AN:

251386

AF XY:

0.195

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 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

African (AFR)

AF:

0.0933

AC:

3125

AN:

33480

American (AMR)

AF:

0.419

AC:

18742

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

6663

AN:

26134

East Asian (EAS)

AF:

0.451

AC:

17892

AN:

39700

South Asian (SAS)

AF:

0.150

AC:

12959

AN:

86256

European-Finnish (FIN)

AF:

0.150

AC:

7987

AN:

53420

Middle Eastern (MID)

AF:

0.146

AC:

841

AN:

5768

European-Non Finnish (NFE)

AF:

0.128

AC:

142813

AN:

1111996

Other (OTH)

AF:

0.164

AC:

9918

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

12398

24797

37195

49594

61992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5392

10784

16176

21568

26960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.156

AC:

23736

AN:

152154

Hom.:

2457

Cov.:

AF XY:

0.161

AC XY:

12007

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0929

AC:

3858

AN:

41532

American (AMR)

AF:

0.298

AC:

4554

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

896

AN:

3470

East Asian (EAS)

AF:

0.456

AC:

2351

AN:

5156

South Asian (SAS)

AF:

0.155

AC:

746

AN:

4820

European-Finnish (FIN)

AF:

0.148

AC:

1569

AN:

10596

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9190

AN:

67990

Other (OTH)

AF:

0.177

AC:

374

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

983

1966

2949

3932

4915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.150

Hom.:

3226

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.6

(source)

DANN

Benign

0.66

PhyloP100

0.99

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=75/25

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over