7-139647254-G-A

Position:

• chr7-139647254-G-A

Variant summary

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

The NM_022740.5(HIPK2):​c.1104-15529C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,780 control chromosomes in the GnomAD database, including 17,220 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 0.46 (17220 hom., cov: 30)
• Consequence: HIPK2 NM_022740.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

Genes affected

HIPK2 (HGNC:14402): (homeodomain interacting protein kinase 2) This gene encodes a conserved serine/threonine kinase that is a member of the homeodomain-interacting protein kinase family. The encoded protein interacts with homeodomain transcription factors and many other transcription factors such as p53, and can function as both a corepressor and a coactivator depending on the transcription factor and its subcellular localization. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIPK2	NM_022740.5	c.1104-15529C>T		intron_variant		ENST00000406875.8	NP_073577.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIPK2	ENST00000406875.8	c.1104-15529C>T		intron_variant		1	NM_022740.5	ENSP00000385571	A2
HIPK2	ENST00000428878.6	c.1104-15529C>T		intron_variant		1		ENSP00000413724	P4
HIPK2	ENST00000342645.7	c.1083-15529C>T		intron_variant		5		ENSP00000343108

Frequencies

GnomAD3 genomes AF: 0.462 AC: 69999 AN: 151662 Hom.: 17190 Cov.: 30

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.462 AC: 70077 AN: 151780 Hom.: 17220 Cov.: 30 AF XY: 0.455 AC XY: 33749 AN XY: 74156

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.0854

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.438

Alfa AF: 0.449 Hom.: 11341

Bravo AF: 0.453

Asia WGS AF: 0.265 AC: 925 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	0.20
DANN	Benign	0.45

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: rs1464798; hg19: chr7-139332000;