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GeneBe

3-49032245-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_198880.3(QRICH1):c.2076G>A(p.Thr692=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,613,750 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

QRICH1
NM_198880.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-49032245-C-T is Benign according to our data. Variant chr3-49032245-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653818.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.14 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00123 (187/152292) while in subpopulation NFE AF= 0.00207 (141/68016). AF 95% confidence interval is 0.00179. There are 0 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 187 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
QRICH1NM_198880.3 linkuse as main transcriptc.2076G>A p.Thr692= synonymous_variant 9/10 ENST00000395443.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
QRICH1ENST00000395443.7 linkuse as main transcriptc.2076G>A p.Thr692= synonymous_variant 9/101 NM_198880.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00123
AC:
187
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00207
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00122
AC:
307
AN:
251462
Hom.:
0
AF XY:
0.00116
AC XY:
157
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00162
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00207
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00223
AC:
3266
AN:
1461458
Hom.:
6
Cov.:
31
AF XY:
0.00211
AC XY:
1531
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.00186
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.00278
Gnomad4 OTH exome
AF:
0.00121
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00123
AC:
187
AN:
152292
Hom.:
0
Cov.:
32
AF XY:
0.00114
AC XY:
85
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.00207
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.00221
Hom.:
0
Bravo
AF:
0.00147
EpiCase
AF:
0.00169
EpiControl
AF:
0.00184

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 submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2023QRICH1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
9.8
Dann
Benign
0.66

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.

Other links and lift over

dbSNP: rs76812435; hg19: chr3-49069678; API