NM_198880.3:c.1895+54G>A

Variant names:

• chr3-49033066-C-T
• rs4974081
• NM_198880.3:c.1895+54G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 23 publications found

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)

ENSG00000290315 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198880.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QRICH1	NM_198880.3	MANE Select	c.1895+54G>A		intron	N/A	NP_942581.1
	QRICH1	NM_001320580.2		c.1895+54G>A		intron	N/A	NP_001307509.1
	QRICH1	NM_001320581.2		c.1895+54G>A		intron	N/A	NP_001307510.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QRICH1	ENST00000395443.7	TSL:1 MANE Select	c.1895+54G>A		intron	N/A	ENSP00000378830.2
	ENSG00000290315	ENST00000703936.1		c.1895+54G>A		intron	N/A	ENSP00000515567.1
	QRICH1	ENST00000477021.1	TSL:3	n.136G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124441 AN: 152064 Hom.: 51280 Cov.: 32

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.: 15 AF XY: 0.791 AC XY: 452108 AN XY: 571302

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

GnomAD4 genome AF: 0.818 AC: 124548 AN: 152182 Hom.: 51327 Cov.: 32 AF XY: 0.825 AC XY: 61361 AN XY: 74396

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.64
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4974081; hg19: chr3-49070499;