1-113969461-G-C

Position:

• chr1-113969461-G-C

Variant summary

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

The NM_198268.3(HIPK1):​c.2772-495G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,066 control chromosomes in the GnomAD database, including 4,348 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 0.24 (4348 hom., cov: 32)
• Consequence: HIPK1 NM_198268.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

Genes affected

HIPK1 (HGNC:19006): (homeodomain interacting protein kinase 1) The protein encoded by this gene belongs to the Ser/Thr family of protein kinases and HIPK subfamily. It phosphorylates homeodomain transcription factors and may also function as a co-repressor for homeodomain transcription factors. Alternative splicing results in four transcript variants encoding four distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIPK1	NM_198268.3	c.2772-495G>C		intron_variant		ENST00000426820.7	NP_938009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIPK1	ENST00000426820.7	c.2772-495G>C		intron_variant		2	NM_198268.3	ENSP00000407442	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36003 AN: 151948 Hom.: 4344 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.237 AC: 36030 AN: 152066 Hom.: 4348 Cov.: 32 AF XY: 0.239 AC XY: 17791 AN XY: 74316

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.216

Alfa AF: 0.249 Hom.: 642

Bravo AF: 0.229

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.3
DANN	Benign	0.71

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: rs11102709; hg19: chr1-114512083;