rs276219

chr10-104327754-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001272013.2(ITPRIP):c.-14+10492T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,084 control chromosomes in the GnomAD database, including 14,724 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 0.40 (14724 hom., cov: 32)
• Consequence: ITPRIP NM_001272013.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

Genes affected

ITPRIP (HGNC:29370): (inositol 1,4,5-trisphosphate receptor interacting protein) This gene encodes a membrane-associated protein that binds the inositol 1,4,5-trisphosphate receptor (ITPR). The encoded protein enhances the sensitivity of ITPR to intracellular calcium signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPRIP	NM_001272013.2	c.-14+10492T>C		intron_variant		ENST00000337478.3
ITPRIP	NM_001272012.2	c.-14+1111T>C		intron_variant
ITPRIP	NM_033397.4	c.-14+5584T>C		intron_variant
ITPRIP	XM_005270257.3	c.2+500T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPRIP	ENST00000337478.3	c.-14+10492T>C		intron_variant		1	NM_001272013.2	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61410 AN: 151962 Hom.: 14684 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.404 AC: 61498 AN: 152084 Hom.: 14724 Cov.: 32 AF XY: 0.400 AC XY: 29712 AN XY: 74330

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.375

Alfa AF: 0.322 Hom.: 16997

Bravo AF: 0.416

Asia WGS AF: 0.266 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.2
Dann	Benign	0.43

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: rs276219; hg19: chr10-106087512;