Genetic Variant ERBIN:p.Glu22Asp (chr5-65992784-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001253697.2(ERBIN):c.66G>C(p.Glu22Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E22K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ERBIN
NM_001253697.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

Publications

0 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 Gene-Disease associations (from GenCC):

autosomal dominant combined immunodeficiency due to ERBIN deficiency
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ERBIN links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29097545).

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	UniProt
ERBIN	NM_001253697.2	MANE Select	c.66G>C	p.Glu22Asp	missense	Exon 3 of 26	NP_001240626.1	Q96RT1-1
ERBIN	NM_001253699.2		c.66G>C	p.Glu22Asp	missense	Exon 3 of 26	NP_001240628.1	Q96RT1-8
ERBIN	NM_018695.4		c.66G>C	p.Glu22Asp	missense	Exon 3 of 25	NP_061165.1	Q96RT1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERBIN	ENST00000284037.10	TSL:1 MANE Select	c.66G>C	p.Glu22Asp	missense	Exon 3 of 26	ENSP00000284037.4	Q96RT1-1
ERBIN	ENST00000506030.6	TSL:1	c.66G>C	p.Glu22Asp	missense	Exon 3 of 26	ENSP00000426632.1	Q96RT1-8
ERBIN	ENST00000380943.6	TSL:1	c.66G>C	p.Glu22Asp	missense	Exon 3 of 25	ENSP00000370330.2	Q96RT1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

Eigen

Benign

0.13

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.018

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.97

PhyloP100

3.2

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-2.0

REVEL

Benign

0.19

Sift

Benign

0.043

Sift4G

Benign

0.066

Polyphen

1.0

Vest4

0.56

MutPred

0.22

Loss of sheet (P = 0.0817)

MVP

0.082

MPC

0.39

ClinPred

0.89

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.37

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over