rs72639216

Variant names:

• chr3-49029748-G-T
• rs72639216
• NM_198880.3:c.*704C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017730.4(QRICH1):​c.*704C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 324,582 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: QRICH1 NM_017730.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 0 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=-0.51).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000256 (39/152196) while in subpopulation AFR AF = 0.000843 (35/41524). AF 95% confidence interval is 0.000622. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 39 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017730.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QRICH1	NM_198880.3	MANE Select	c.*704C>A		3_prime_UTR	Exon 10 of 10	NP_942581.1
	QRICH1	NM_001320580.2		c.*704C>A		3_prime_UTR	Exon 11 of 11	NP_001307509.1
	QRICH1	NM_001320581.2		c.*704C>A		3_prime_UTR	Exon 11 of 11	NP_001307510.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QRICH1	ENST00000395443.7	TSL:1 MANE Select	c.*704C>A		3_prime_UTR	Exon 10 of 10	ENSP00000378830.2
	ENSG00000290315	ENST00000703936.1		c.2139-942C>A		intron	N/A	ENSP00000515567.1
	QRICH1	ENST00000887075.1		c.*704C>A		3_prime_UTR	Exon 10 of 10	ENSP00000557134.1

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152080 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000348 AC: 6 AN: 172386 Hom.: 0 Cov.: 0 AF XY: 0.0000322 AC XY: 3 AN XY: 93136

African (AFR) AF: 0.000580 AC: 3 AN: 5168

American (AMR) AF: 0.00 AC: 0 AN: 5290

Ashkenazi Jewish (ASJ) AF: 0.000228 AC: 1 AN: 4392

East Asian (EAS) AF: 0.00 AC: 0 AN: 6554

South Asian (SAS) AF: 0.00 AC: 0 AN: 32826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 660

European-Non Finnish (NFE) AF: 0.00000998 AC: 1 AN: 100220

Other (OTH) AF: 0.000118 AC: 1 AN: 8482

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74394

African (AFR) AF: 0.000843 AC: 35 AN: 41524

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		2.5
PromoterAI		0.029	Neutral

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: rs72639216; hg19: chr3-49067181;