Variant 8-673400-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207332.3(ERICH1):c.952G>A(p.Gly318Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ERICH1
NM_207332.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

ERICH1 (HGNC:27234): (glutamate rich 1)

ERICH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055571437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH1	NM_207332.3 linkuse as main transcript	c.952G>A	p.Gly318Arg	missense_variant	4/6	ENST00000262109.8	NP_997215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ERICH1	ENST00000262109.8 linkuse as main transcript	c.952G>A	p.Gly318Arg	missense_variant	4/6	1	NM_207332.3	ENSP00000262109	P2
ERICH1	ENST00000522893.1 linkuse as main transcript	c.259G>A	p.Gly87Arg	missense_variant	1/2	1		ENSP00000428556
ERICH1	ENST00000522706.5 linkuse as main transcript	c.670G>A	p.Gly224Arg	missense_variant	2/4	5		ENSP00000428635	A2
ERICH1	ENST00000518895.1 linkuse as main transcript	n.63G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000400

AC:

AN:

150132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000738

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251444

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000399

AC:

AN:

150256

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73356

show subpopulations

Gnomad4 AFR

AF:

0.0000736

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000474

Hom.:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.952G>A (p.G318R) alteration is located in exon 4 (coding exon 4) of the ERICH1 gene. This alteration results from a G to A substitution at nucleotide position 952, causing the glycine (G) at amino acid position 318 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.4

DANN

Benign

0.90

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.078

Sift

Benign

0.55

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.91

P;P

Vest4

0.14

MutPred

0.30

.;Loss of catalytic residue at G318 (P = 0.0482);

MVP

0.16

MPC

0.012

ClinPred

0.018

GERP RS

-1.8

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

Varity_R

0.032

gMVP

0.013

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