Variant 5-66021353-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001253697.2(ERBIN):c.565C>T(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 1,599,706 control chromosomes in the GnomAD database, including 555,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42667 hom., cov: 32)

Exomes 𝑓: 0.84 ( 512421 hom. )

Consequence

ERBIN
NM_001253697.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.260

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 5-66021353-C-T is Benign according to our data. Variant chr5-66021353-C-T is described in ClinVar as [Benign]. Clinvar id is 1169278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.855 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.565C>T	p.Leu189Leu	synonymous_variant	8/26	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.565C>T	p.Leu189Leu	synonymous_variant	8/26	1	NM_001253697.2	ENSP00000284037.4		Q96RT1-1

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111448

AN:

151746

Hom.:

42661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.837

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.841

Gnomad FIN

AF:

0.851

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.861

Gnomad OTH

AF:

0.731

GnomAD3 exomes

AF:

0.761

AC:

187314

AN:

246270

Hom.:

74245

AF XY:

0.779

AC XY:

103961

AN XY:

133412

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.729

Gnomad EAS exome

AF:

0.514

Gnomad SAS exome

AF:

0.852

Gnomad FIN exome

AF:

0.850

Gnomad NFE exome

AF:

0.861

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

AF:

0.836

AC:

1209679

AN:

1447842

Hom.:

512421

Cov.:

AF XY:

0.837

AC XY:

603518

AN XY:

720736

show subpopulations

Gnomad4 AFR exome

AF:

0.515

Gnomad4 AMR exome

AF:

0.553

Gnomad4 ASJ exome

AF:

0.730

Gnomad4 EAS exome

AF:

0.547

Gnomad4 SAS exome

AF:

0.847

Gnomad4 FIN exome

AF:

0.850

Gnomad4 NFE exome

AF:

0.869

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.734

AC:

111471

AN:

151864

Hom.:

42667

Cov.:

AF XY:

0.732

AC XY:

54326

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.534

Gnomad4 AMR

AF:

0.658

Gnomad4 ASJ

AF:

0.729

Gnomad4 EAS

AF:

0.541

Gnomad4 SAS

AF:

0.842

Gnomad4 FIN

AF:

0.851

Gnomad4 NFE

AF:

0.861

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.794

Hom.:

28085

Bravo

AF:

0.706

Asia WGS

AF:

0.723

AC:

2515

AN:

3474

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

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 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 80. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

8.4

DANN

Benign

0.75

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