rs7545038

Positions:

• chr1-113936808-A-G
• chr1-113936808-A-T

Variant summary

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

The NM_198268.3(HIPK1):​c.-2-3574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,212 control chromosomes in the GnomAD database, including 45,264 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 0.76 (45264 hom., cov: 33)
• Consequence: HIPK1 NM_198268.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIPK1	NM_198268.3	c.-2-3574A>G		intron_variant		ENST00000426820.7	NP_938009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIPK1	ENST00000426820.7	c.-2-3574A>G		intron_variant		2	NM_198268.3	ENSP00000407442	P1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116252 AN: 152094 Hom.: 45212 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.764 AC: 116362 AN: 152212 Hom.: 45264 Cov.: 33 AF XY: 0.761 AC XY: 56627 AN XY: 74392

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.740

Alfa AF: 0.707 Hom.: 15014

Bravo AF: 0.774

Asia WGS AF: 0.732 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.63
DANN	Benign	0.82

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: rs7545038; hg19: chr1-114479430;