3-49732599-G-A

Variant names:

• chr3-49732599-G-A
• rs3749237
• NM_153273.4:c.616+192C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153273.4(IP6K1):​c.616+192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,048 control chromosomes in the GnomAD database, including 5,546 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 0.26 (5546 hom., cov: 32)
• Consequence: IP6K1 NM_153273.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 36 publications found

Genes affected

IP6K1 (HGNC:18360): (inositol hexakisphosphate kinase 1) This gene encodes a member of the inositol phosphokinase family. The encoded protein may be responsible for the conversion of inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). It may also convert 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2011]

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 (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153273.4. 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
	IP6K1	NM_153273.4	MANE Select	c.616+192C>T		intron	N/A	NP_695005.1
	IP6K1	NM_001242829.2		c.616+192C>T		intron	N/A	NP_001229758.1
	IP6K1	NM_001006115.3		c.121+192C>T		intron	N/A	NP_001006115.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IP6K1	ENST00000321599.9	TSL:1 MANE Select	c.616+192C>T		intron	N/A	ENSP00000323780.4
	IP6K1	ENST00000613416.4	TSL:5	c.616+192C>T		intron	N/A	ENSP00000482032.1
	IP6K1	ENST00000395238.5	TSL:3	c.121+192C>T		intron	N/A	ENSP00000378659.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39950 AN: 151928 Hom.: 5537 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.263 AC: 39969 AN: 152048 Hom.: 5546 Cov.: 32 AF XY: 0.259 AC XY: 19221 AN XY: 74314

African (AFR) AF: 0.212 AC: 8804 AN: 41472

American (AMR) AF: 0.217 AC: 3317 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.169 AC: 875 AN: 5180

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4818

European-Finnish (FIN) AF: 0.242 AC: 2554 AN: 10540

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21179 AN: 67988

Other (OTH) AF: 0.269 AC: 568 AN: 2112

Alfa AF: 0.279 Hom.: 5183

Bravo AF: 0.257

Asia WGS AF: 0.305 AC: 1058 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	9.4
DANN	Benign	0.77
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3749237; hg19: chr3-49770032;