Variant chr1-74606593-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001002912.5(ERICH3):c.1489+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,590,670 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 47 hom. )

Consequence

ERICH3
NM_001002912.5 splice_region, intron

Scores

Splicing: ADA: 0.00009227

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0740

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-74606593-T-C is Benign according to our data. Variant chr1-74606593-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638881.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-74606593-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00474 (6819/1438556) while in subpopulation MID AF= 0.0437 (245/5612). AF 95% confidence interval is 0.0392. There are 47 homozygotes in gnomad4_exome. There are 3470 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ERICH3	NM_001002912.5 link	c.1489+8A>G	splice_region_variant, intron_variant	ENST00000326665.10	NP_001002912.4	Q5RHP9-1
ERICH3	XM_017000275.2 link	c.1483+8A>G	splice_region_variant, intron_variant		XP_016855764.1
ERICH3-AS1	NR_121670.1 link	n.174-8613T>C	intron_variant
ERICH3-AS1	NR_121671.1 link	n.81-8613T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ERICH3	ENST00000326665.10 link	c.1489+8A>G	splice_region_variant, intron_variant	5	NM_001002912.5	ENSP00000322609.5	Q5RHP9-1
ERICH3	ENST00000420661.6 link	c.898+8A>G	splice_region_variant, intron_variant	1		ENSP00000398581.2	Q5RHP9-3
ERICH3-AS1	ENST00000612390.4 link	n.81-8613T>C	intron_variant	1
ERICH3-AS1	ENST00000416017.1 link	n.174-8613T>C	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00447

AC:

680

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00630

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.00605

Gnomad OTH

AF:

0.00720

GnomAD3 exomes

AF:

0.00553

AC:

1308

AN:

236432

Hom.:

AF XY:

0.00550

AC XY:

703

AN XY:

127780

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00635

Gnomad ASJ exome

AF:

0.0158

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00320

Gnomad FIN exome

AF:

0.00210

Gnomad NFE exome

AF:

0.00703

Gnomad OTH exome

AF:

0.00969

GnomAD4 exome

AF:

0.00474

AC:

6819

AN:

1438556

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

3470

AN XY:

713854

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00681

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00301

Gnomad4 FIN exome

AF:

0.00193

Gnomad4 NFE exome

AF:

0.00464

Gnomad4 OTH exome

AF:

0.00627

GnomAD4 genome

AF:

0.00445

AC:

677

AN:

152114

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

293

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00630

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00605

Gnomad4 OTH

AF:

0.00713

Alfa

AF:

0.00631

Hom.:

Bravo

AF:

0.00478

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00896

EpiControl

AF:

0.00962

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

May 01, 2023

ERICH3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.93

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000092

dbscSNV1_RF

Benign

0.0

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