Genetic Variant NM_198880.3:c.1895+54G>A (chr3-49033066-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198880.3(QRICH1):c.1895+54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 1,312,620 control chromosomes in the GnomAD database, including 414,433 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.82 ( 51327 hom., cov: 32)

Exomes 𝑓: 0.79 ( 363106 hom. )

Consequence

QRICH1
NM_198880.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.319

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Ververi-Brady syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

QRICH1 links:

ENSG00000290315 (HGNC:):

ENSG00000290315 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
QRICH1	NM_198880.3 link	c.1895+54G>A		intron_variant	Intron 7 of 9	ENST00000395443.7	NP_942581.1	Q2TAL8A1L3Z9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
QRICH1	ENST00000395443.7 link	c.1895+54G>A		intron_variant	Intron 7 of 9	1	NM_198880.3	ENSP00000378830.2		Q2TAL8
ENSG00000290315	ENST00000703936.1 link	c.1895+54G>A		intron_variant	Intron 7 of 21			ENSP00000515567.1		A0A994J749

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124441

AN:

152064

Hom.:

51280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.869

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.942

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.803

Gnomad NFE

AF:

0.752

Gnomad OTH

AF:

0.803

GnomAD4 exome

AF:

0.788

AC:

914826

AN:

1160438

Hom.:

363106

Cov.:

AF XY:

0.791

AC XY:

452108

AN XY:

571302

show subpopulations

African (AFR)

AF:

0.887

AC:

21416

AN:

24142

American (AMR)

AF:

0.890

AC:

19781

AN:

22216

Ashkenazi Jewish (ASJ)

AF:

0.870

AC:

15405

AN:

17716

East Asian (EAS)

AF:

1.00

AC:

32758

AN:

32766

South Asian (SAS)

AF:

0.936

AC:

53304

AN:

56954

European-Finnish (FIN)

AF:

0.793

AC:

38564

AN:

48634

Middle Eastern (MID)

AF:

0.794

AC:

3845

AN:

4844

European-Non Finnish (NFE)

AF:

0.763

AC:

690471

AN:

904610

Other (OTH)

AF:

0.809

AC:

39282

AN:

48556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

9097

18194

27290

36387

45484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16930

33860

50790

67720

84650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.818

AC:

124548

AN:

152182

Hom.:

51327

Cov.:

AF XY:

0.825

AC XY:

61361

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.882

AC:

36631

AN:

41534

American (AMR)

AF:

0.845

AC:

12923

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.869

AC:

3017

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5178

AN:

5184

South Asian (SAS)

AF:

0.942

AC:

4545

AN:

4826

European-Finnish (FIN)

AF:

0.809

AC:

8558

AN:

10582

Middle Eastern (MID)

AF:

0.798

AC:

233

AN:

292

European-Non Finnish (NFE)

AF:

0.752

AC:

51092

AN:

67966

Other (OTH)

AF:

0.806

AC:

1702

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1164

2328

3492

4656

5820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.787

Hom.:

83684

Bravo

AF:

0.824

Asia WGS

AF:

0.965

AC:

3355

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over