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GeneBe

chr3-49030617-G-A

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

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

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]

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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 UniProt
QRICH1NM_198880.3 linkuse as main transcriptc.2166C>T p.Asp722= synonymous_variant 10/10 ENST00000395443.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
QRICH1ENST00000395443.7 linkuse as main transcriptc.2166C>T p.Asp722= synonymous_variant 10/101 NM_198880.3 P1

Frequencies

GnomAD3 genomes
AF:
0.00131
AC:
200
AN:
152204
Hom.:
0
Cov.:
32
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.:
0
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.:
14
Cov.:
31
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.:
0
Cov.:
32
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.:
2
Bravo
AF:
0.00162
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2024QRICH1: BP4, BP7, BS1 -
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -
QRICH1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 28, 2019This 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.

Other links and lift over

dbSNP: rs146971607; hg19: chr3-49068050; API