7-139674341-C-T

Variant names:

• chr7-139674341-C-T
• rs10954654
• NM_022740.5:c.1103+41591G>A

Variant summary

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

The NM_022740.5(HIPK2):​c.1103+41591G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,042 control chromosomes in the GnomAD database, including 6,371 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 0.27 (6371 hom., cov: 31)
• Consequence: HIPK2 NM_022740.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIPK2	NM_022740.5	c.1103+41591G>A		intron_variant	Intron 2 of 14	ENST00000406875.8	NP_073577.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIPK2	ENST00000406875.8	c.1103+41591G>A		intron_variant	Intron 2 of 14	1	NM_022740.5	ENSP00000385571.3
HIPK2	ENST00000428878.6	c.1103+41591G>A		intron_variant	Intron 2 of 14	1		ENSP00000413724.2
HIPK2	ENST00000342645.7	c.1082+41591G>A		intron_variant	Intron 1 of 10	5		ENSP00000343108.7

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40669 AN: 151924 Hom.: 6358 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.268 AC: 40697 AN: 152042 Hom.: 6371 Cov.: 31 AF XY: 0.274 AC XY: 20406 AN XY: 74348

African (AFR) AF: 0.177 AC: 7321 AN: 41456

American (AMR) AF: 0.251 AC: 3839 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1091 AN: 3468

East Asian (EAS) AF: 0.682 AC: 3522 AN: 5164

South Asian (SAS) AF: 0.563 AC: 2713 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2822 AN: 10574

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18522 AN: 67978

Other (OTH) AF: 0.290 AC: 611 AN: 2110

Alfa AF: 0.269 Hom.: 3451

Bravo AF: 0.261

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.78
PhyloP100		-0.65

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: rs10954654; hg19: chr7-139359087;