rs36303

chr5-66054546-A-Gchr5-66054546-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001253697.2(ERBIN):c.3228A>G(p.Arg1076=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.995

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]

ACMG classification

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	UniProt
ERBIN	NM_001253697.2	c.3228A>G	p.Arg1076=	synonymous_variant	21/26	ENST00000284037.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERBIN	ENST00000284037.10	c.3228A>G	p.Arg1076=	synonymous_variant	21/26	1	NM_001253697.2	A1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23704 AN: 152036 Hom.: 2445 Cov.: 32

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

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.: 34 AF XY: 0.151 AC XY: 109568 AN XY: 727234

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.: 32 AF XY: 0.161 AC XY: 12007 AN XY: 74376

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

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

Other links and lift over

dbSNP: rs36303; hg19: chr5-65350374; COSMIC: COSV52309806; COSMIC: COSV52309806;