rs2273749

Variant names:

• chr10-119805503-C-A
• rs2273749
• NM_014937.4:c.1319+42C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-119805503-C-A
• chr10-119805503-C-G
• chr10-119805503-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014937.4(INPP5F):​c.1319+42C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000847 in 1,180,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: INPP5F NM_014937.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 0 publications found

Genes affected

INPP5F (HGNC:17054): (inositol polyphosphate-5-phosphatase F) The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase and contains a Sac domain. The activity of this protein is specific for phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

ENSG00000293336 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014937.4. 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
	INPP5F	NM_014937.4	MANE Select	c.1319+42C>A		intron	N/A	NP_055752.1
	INPP5F	NM_001441000.1		c.1319+42C>A		intron	N/A	NP_001427929.1
	INPP5F	NM_001441001.1		c.1268+42C>A		intron	N/A	NP_001427930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	ENST00000650623.2	MANE Select	c.1319+42C>A		intron	N/A	ENSP00000497527.1
	INPP5F	ENST00000648262.1		c.1133+42C>A		intron	N/A	ENSP00000496843.1
	INPP5F	ENST00000647699.1		c.1031+42C>A		intron	N/A	ENSP00000497772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.47e-7 AC: 1 AN: 1180674 Hom.: 0 Cov.: 15 AF XY: 0.00000166 AC XY: 1 AN XY: 601064

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27600

American (AMR) AF: 0.00 AC: 0 AN: 43314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24316

East Asian (EAS) AF: 0.00 AC: 0 AN: 38360

South Asian (SAS) AF: 0.00 AC: 0 AN: 79736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5194

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 858570

Other (OTH) AF: 0.00 AC: 0 AN: 51030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2273749; hg19: chr10-121565015;