chr3-4493454-G-A

Variant names:

• chr3-4493454-G-A
• rs577585180
• NM_001378452.1:c.-244G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS1

The NM_001378452.1(ITPR1):​c.-244G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000722 in 152,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITPR1 NM_001378452.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.39
• Publications: 0 publications found

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-DT (HGNC:44470): (ITPR1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 3-4493454-G-A is Benign according to our data. Variant chr3-4493454-G-A is described in ClinVar as Benign. ClinVar VariationId is 345332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000722 (11/152302) while in subpopulation EAS AF = 0.00212 (11/5188). AF 95% confidence interval is 0.00119. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378452.1. 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
	ITPR1	NM_001378452.1	MANE Select	c.-244G>A		5_prime_UTR	Exon 1 of 62	NP_001365381.1	Q14643-1
	ITPR1	NM_001168272.2		c.-244G>A		5_prime_UTR	Exon 1 of 61	NP_001161744.1	Q14643-2
	ITPR1	NM_001099952.4		c.-244G>A		5_prime_UTR	Exon 1 of 59	NP_001093422.2	Q14643-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPR1	ENST00000649015.2	MANE Select	c.-244G>A		5_prime_UTR	Exon 1 of 62	ENSP00000497605.1	Q14643-1
	ITPR1	ENST00000354582.12	TSL:5	c.-244G>A		5_prime_UTR	Exon 1 of 62	ENSP00000346595.8	A0A3F2YNW8
	ITPR1	ENST00000648266.1		c.-244G>A		5_prime_UTR	Exon 1 of 62	ENSP00000498014.1	A0A3B3IU04

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2206 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1218

African (AFR) AF: 0.00 AC: 0 AN: 14

American (AMR) AF: 0.00 AC: 0 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12

East Asian (EAS) AF: 0.00 AC: 0 AN: 24

South Asian (SAS) AF: 0.00 AC: 0 AN: 858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 560

Other (OTH) AF: 0.00 AC: 0 AN: 98

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal dominant cerebellar ataxia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		2.4
PromoterAI		0.18	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs577585180; hg19: chr3-4535138;