NM_001378452.1:c.6808+4G>C

Variant names:

• chr3-4788143-G-C
• NM_001378452.1:c.6808+4G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378452.1(ITPR1):​c.6808+4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ITPR1 NM_001378452.1 splice_region, intron
• Scores: Splicing: ADA: 0.0003734
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR1	NM_001378452.1	c.6808+4G>C		splice_region_variant, intron_variant	Intron 52 of 61	ENST00000649015.2	NP_001365381.1
ITPR1	NM_001168272.2	c.6763+4G>C		splice_region_variant, intron_variant	Intron 51 of 60		NP_001161744.1
ITPR1	NM_001099952.4	c.6664+4G>C		splice_region_variant, intron_variant	Intron 49 of 58		NP_001093422.2
ITPR1	NM_002222.7	c.6619+4G>C		splice_region_variant, intron_variant	Intron 48 of 57		NP_002213.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR1	ENST00000649015.2	c.6808+4G>C		splice_region_variant, intron_variant	Intron 52 of 61		NM_001378452.1	ENSP00000497605.1
ITPR1	ENST00000354582.12	c.6784+4G>C		splice_region_variant, intron_variant	Intron 52 of 61	5		ENSP00000346595.8
ITPR1	ENST00000648266.1	c.6781+4G>C		splice_region_variant, intron_variant	Intron 52 of 61			ENSP00000498014.1
ITPR1	ENST00000650294.1	c.6766+4G>C		splice_region_variant, intron_variant	Intron 51 of 60			ENSP00000498056.1
ITPR1	ENST00000443694.5	c.6763+4G>C		splice_region_variant, intron_variant	Intron 51 of 60	1		ENSP00000401671.2
ITPR1	ENST00000648309.1	c.6736+4G>C		splice_region_variant, intron_variant	Intron 49 of 58			ENSP00000497026.1
ITPR1	ENST00000357086.10	c.6664+4G>C		splice_region_variant, intron_variant	Intron 49 of 58	1		ENSP00000349597.4
ITPR1	ENST00000456211.8	c.6619+4G>C		splice_region_variant, intron_variant	Intron 48 of 57	1		ENSP00000397885.2
ITPR1	ENST00000648038.1	c.4570+4G>C		splice_region_variant, intron_variant	Intron 32 of 41			ENSP00000497872.1
ITPR1	ENST00000648431.1	c.4108+4G>C		splice_region_variant, intron_variant	Intron 30 of 38			ENSP00000498149.1
ITPR1	ENST00000648212.1	c.3715+4G>C		splice_region_variant, intron_variant	Intron 28 of 38			ENSP00000498022.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1442016 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 715128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00037
dbscSNV1_RF	Benign	0.16
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-4829827;