Variant 1-74606870-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001002912.5(ERICH3):c.1220C>T(p.Pro407Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0062 in 1,611,672 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P407S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 39 hom. )

Consequence

ERICH3
NM_001002912.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.07

Variant links:

Genes affected

ERICH3 (HGNC:25346): (glutamate rich 3)

ERICH3 links:

ERICH3-AS1 (HGNC:41093): (ERICH3 antisense RNA 1)

ERICH3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-74606870-G-A is Benign according to our data. Variant chr1-74606870-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638882.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERICH3	NM_001002912.5 link	c.1220C>T	p.Pro407Leu	missense_variant	10/15	ENST00000326665.10	NP_001002912.4	Q5RHP9-1
ERICH3	XM_017000275.2 link	c.1214C>T	p.Pro405Leu	missense_variant	10/14		XP_016855764.1
ERICH3-AS1	NR_121670.1 link	n.174-8336G>A		intron_variant
ERICH3-AS1	NR_121671.1 link	n.81-8336G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ERICH3	ENST00000326665.10 link	c.1220C>T	p.Pro407Leu	missense_variant	10/15	5	NM_001002912.5	ENSP00000322609.5	Q5RHP9-1
ERICH3	ENST00000420661.6 link	c.629C>T	p.Pro210Leu	missense_variant	5/7	1		ENSP00000398581.2	Q5RHP9-3
ERICH3-AS1	ENST00000612390.4 link	n.81-8336G>A		intron_variant		1
ERICH3-AS1	ENST00000416017.1 link	n.174-8336G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00471

AC:

714

AN:

151708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00642

Gnomad OTH

AF:

0.00338

GnomAD3 exomes

AF:

0.00523

AC:

1307

AN:

249790

Hom.:

AF XY:

0.00522

AC XY:

705

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.000558

Gnomad AMR exome

AF:

0.00181

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00188

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.00658

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

AF:

0.00635

AC:

9274

AN:

1459846

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

4412

AN XY:

726220

show subpopulations

Gnomad4 AFR exome

AF:

0.000992

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00206

Gnomad4 FIN exome

AF:

0.0165

Gnomad4 NFE exome

AF:

0.00704

Gnomad4 OTH exome

AF:

0.00451

GnomAD4 genome

AF:

0.00470

AC:

714

AN:

151826

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

358

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.0188

Gnomad4 NFE

AF:

0.00642

Gnomad4 OTH

AF:

0.00334

Alfa

AF:

0.00515

Hom.:

Bravo

AF:

0.00354

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00518

AC:

629

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00486

EpiControl

AF:

0.00462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ERICH3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.032

D;D

Polyphen

0.12

B;B

Vest4

0.14

MVP

0.22

MPC

0.020

ClinPred

0.058

GERP RS

4.2

Varity_R

0.17

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.36

Position offset: -19

DS_AL_spliceai

0.20

Position offset: 32

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