10-104327754-A-G

Variant names:

• chr10-104327754-A-G
• rs276219
• NM_001272013.2:c.-14+10492T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ITPRIP-AS1 (HGNC:54100): (ITPRIP antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001272013.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIP	NM_001272013.2	MANE Select	c.-14+10492T>C		intron	N/A	NP_001258942.1
	ITPRIP	NM_001272012.2		c.-14+1111T>C		intron	N/A	NP_001258941.1
	ITPRIP	NM_033397.4		c.-14+5584T>C		intron	N/A	NP_203755.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIP	ENST00000337478.3	TSL:1 MANE Select	c.-14+10492T>C		intron	N/A	ENSP00000337178.1
	ITPRIP	ENST00000278071.6	TSL:1	c.-14+5584T>C		intron	N/A	ENSP00000278071.2
	ITPRIP	ENST00000458723.1	TSL:1	c.-14+5584T>C		intron	N/A	ENSP00000414141.1

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

African (AFR) AF: 0.677 AC: 28069 AN: 41466

American (AMR) AF: 0.295 AC: 4520 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1292 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1066 AN: 5170

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4828

European-Finnish (FIN) AF: 0.314 AC: 3323 AN: 10576

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21059 AN: 67960

Other (OTH) AF: 0.375 AC: 791 AN: 2112

Alfa AF: 0.337 Hom.: 40539

Bravo AF: 0.416

Asia WGS AF: 0.266 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.43
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs276219; hg19: chr10-106087512;