3-4493746-G-A

Position:

• chr3-4493746-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001378452.1(ITPR1):​c.-93+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 152,416 control chromosomes in the GnomAD database, including 92 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 0.029 (92 hom., cov: 32)
  • Exomes 𝑓: 0.052 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

Genes affected

ITPR1 (HGNC:6180): (inositol 1,4,5-trisphosphate receptor type 1) This gene encodes an intracellular receptor for inositol 1,4,5-trisphosphate. Upon stimulation by inositol 1,4,5-trisphosphate, this receptor mediates calcium release from the endoplasmic reticulum. Mutations in this gene cause spinocerebellar ataxia type 15, a disease associated with an heterogeneous group of cerebellar disorders. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]

ITPR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0288 (4392/152282) while in subpopulation NFE AF= 0.0464 (3153/68016). AF 95% confidence interval is 0.045. There are 92 homozygotes in gnomad4. There are 2017 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 92 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.-93+141G>A		intron_variant		ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.-93+141G>A		intron_variant			NP_001161744.1
ITPR1	NM_001099952.4	c.-93+141G>A		intron_variant			NP_001093422.2
ITPR1	NM_002222.7	c.-93+141G>A		intron_variant			NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.-93+141G>A		intron_variant			NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.-93+141G>A		intron_variant		5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.-93+141G>A		intron_variant				ENSP00000498014.1
ITPR1	ENST00000650294.1	c.-93+141G>A		intron_variant				ENSP00000498056.1
ITPR1	ENST00000443694.5	c.-93+141G>A		intron_variant		1		ENSP00000401671.2
ITPR1	ENST00000357086.10	c.-93+141G>A		intron_variant		1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.-93+141G>A		intron_variant		1		ENSP00000397885.2

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4390 AN: 152164 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.00948

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.0259

GnomAD4 exome AF: 0.0522 AC: 7 AN: 134 Hom.: 0 AF XY: 0.0463 AC XY: 5 AN XY: 108

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0648

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0288 AC: 4392 AN: 152282 Hom.: 92 Cov.: 32 AF XY: 0.0271 AC XY: 2017 AN XY: 74468

Gnomad4 AFR AF: 0.00946

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00932

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0464

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0229 Hom.: 18

Bravo AF: 0.0290

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs304075; hg19: chr3-4535430;