rs978752

Variant names:

• chr4-142124446-G-A
• rs978752
• NM_001101669.3:c.1893+142C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-142124446-G-A
• chr4-142124446-G-T

Variant summary

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

The NM_001101669.3(INPP4B):​c.1893+142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 679,390 control chromosomes in the GnomAD database, including 15,289 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 0.21 (3482 hom., cov: 32)
  • Exomes 𝑓: 0.21 (11807 hom.)
• Consequence: INPP4B NM_001101669.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 2 publications found

Genes affected

INPP4B (HGNC:6075): (inositol polyphosphate-4-phosphatase type II B) INPP4B encodes the inositol polyphosphate 4-phosphatase type II, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate. There is limited data to suggest that the human type II enzyme is subject to alternative splicing, as has been established for the type I enzyme. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.1893+142C>T		intron_variant	Intron 19 of 25	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.1893+142C>T		intron_variant	Intron 19 of 25	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32244 AN: 151876 Hom.: 3476 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.208 AC: 109629 AN: 527396 Hom.: 11807 AF XY: 0.209 AC XY: 57310 AN XY: 273920

African (AFR) AF: 0.231 AC: 3212 AN: 13892

American (AMR) AF: 0.164 AC: 3291 AN: 20126

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 2227 AN: 13840

East Asian (EAS) AF: 0.0883 AC: 2779 AN: 31460

South Asian (SAS) AF: 0.247 AC: 11261 AN: 45580

European-Finnish (FIN) AF: 0.222 AC: 8284 AN: 37366

Middle Eastern (MID) AF: 0.192 AC: 685 AN: 3572

European-Non Finnish (NFE) AF: 0.216 AC: 72208 AN: 333630

Other (OTH) AF: 0.203 AC: 5682 AN: 27930

GnomAD4 genome AF: 0.212 AC: 32267 AN: 151994 Hom.: 3482 Cov.: 32 AF XY: 0.212 AC XY: 15712 AN XY: 74270

African (AFR) AF: 0.228 AC: 9472 AN: 41472

American (AMR) AF: 0.180 AC: 2738 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3470

East Asian (EAS) AF: 0.113 AC: 581 AN: 5152

South Asian (SAS) AF: 0.258 AC: 1242 AN: 4816

European-Finnish (FIN) AF: 0.216 AC: 2273 AN: 10544

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14644 AN: 67970

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.211 Hom.: 14746

Bravo AF: 0.209

Asia WGS AF: 0.182 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		-0.20
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: rs978752; hg19: chr4-143045599;