rs4974081

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-49033066-C-A
• chr3-49033066-C-G
• chr3-49033066-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198880.3(QRICH1):​c.1895+54G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

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>T		intron	N/A	NP_942581.1
	QRICH1	NM_001320580.2		c.1895+54G>T		intron	N/A	NP_001307509.1
	QRICH1	NM_001320581.2		c.1895+54G>T		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>T		intron	N/A	ENSP00000378830.2
	ENSG00000290315	ENST00000703936.1		c.1895+54G>T		intron	N/A	ENSP00000515567.1
	QRICH1	ENST00000477021.1	TSL:3	n.136G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1162166 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 572114

African (AFR) AF: 0.00 AC: 0 AN: 24158

American (AMR) AF: 0.00 AC: 0 AN: 22232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17728

East Asian (EAS) AF: 0.00 AC: 0 AN: 32766

South Asian (SAS) AF: 0.00 AC: 0 AN: 57000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4852

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 906142

Other (OTH) AF: 0.00 AC: 0 AN: 48620

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.6
DANN	Benign	0.72
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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;