chr1-113936808-A-G

Variant names:

• chr1-113936808-A-G
• rs7545038
• NM_198268.3:c.-2-3574A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198268.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIPK1	NM_198268.3	MANE Select	c.-2-3574A>G		intron	N/A	NP_938009.1
	HIPK1	NM_001369806.1		c.-2-3574A>G		intron	N/A	NP_001356735.1
	HIPK1	NM_001369807.1		c.-2-3574A>G		intron	N/A	NP_001356736.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIPK1	ENST00000426820.7	TSL:2 MANE Select	c.-2-3574A>G		intron	N/A	ENSP00000407442.3
	HIPK1	ENST00000369558.5	TSL:1	c.-2-3574A>G		intron	N/A	ENSP00000358571.1
	HIPK1	ENST00000369559.8	TSL:1	c.-2-3574A>G		intron	N/A	ENSP00000358572.4

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

African (AFR) AF: 0.921 AC: 38243 AN: 41526

American (AMR) AF: 0.714 AC: 10917 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2664 AN: 3472

East Asian (EAS) AF: 0.845 AC: 4380 AN: 5186

South Asian (SAS) AF: 0.600 AC: 2893 AN: 4824

European-Finnish (FIN) AF: 0.719 AC: 7605 AN: 10580

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47293 AN: 68018

Other (OTH) AF: 0.740 AC: 1562 AN: 2112

Alfa AF: 0.710 Hom.: 17352

Bravo AF: 0.774

Asia WGS AF: 0.732 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.63
DANN	Benign	0.82
PhyloP100		-0.63
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: rs7545038; hg19: chr1-114479430;