Variant 3-49030617-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_198880.3(QRICH1):c.2166C>T(p.Asp722=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,596,288 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 14 hom. )

Consequence

QRICH1
NM_198880.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.97

Variant links:

Genes affected

QRICH1 (HGNC:24713): (glutamine rich 1) Enables DNA binding activity. Involved in several processes, including PERK-mediated unfolded protein response; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; and positive regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

QRICH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 3-49030617-G-A is Benign according to our data. Variant chr3-49030617-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 773573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.97 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00131 (199/152322) while in subpopulation AMR AF= 0.00359 (55/15300). AF 95% confidence interval is 0.00284. There are 0 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 199 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRICH1	NM_198880.3 linkuse as main transcript	c.2166C>T	p.Asp722=	synonymous_variant	10/10	ENST00000395443.7	NP_942581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QRICH1	ENST00000395443.7 linkuse as main transcript	c.2166C>T	p.Asp722=	synonymous_variant	10/10	1	NM_198880.3	ENSP00000378830	P1

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

200

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00155

AC:

365

AN:

235872

Hom.:

AF XY:

0.00151

AC XY:

193

AN XY:

127974

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.00242

Gnomad ASJ exome

AF:

0.00551

Gnomad EAS exome

AF:

0.0000581

Gnomad SAS exome

AF:

0.00169

Gnomad FIN exome

AF:

0.0000471

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00125

AC:

1807

AN:

1443966

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

947

AN XY:

717170

show subpopulations

Gnomad4 AFR exome

AF:

0.000676

Gnomad4 AMR exome

AF:

0.00258

Gnomad4 ASJ exome

AF:

0.00463

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00162

Gnomad4 FIN exome

AF:

0.0000565

Gnomad4 NFE exome

AF:

0.000988

Gnomad4 OTH exome

AF:

0.00302

GnomAD4 genome

AF:

0.00131

AC:

199

AN:

152322

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00165

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.00162

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	QRICH1: BP4, BP7, BS1 -

QRICH1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.9

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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