rs4794758

Positions:

• chr17-37720433-T-C

Variant summary

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

The NM_000458.4(HNF1B):​c.1046-9770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,848 control chromosomes in the GnomAD database, including 35,359 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 0.67 (35359 hom., cov: 30)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447

Genes affected

HNF1B (HGNC:11630): (HNF1 homeobox B) This gene encodes a member of the homeodomain-containing superfamily of transcription factors. The protein binds to DNA as either a homodimer, or a heterodimer with the related protein hepatocyte nuclear factor 1-alpha. The gene has been shown to function in nephron development, and regulates development of the embryonic pancreas. Mutations in this gene result in renal cysts and diabetes syndrome and noninsulin-dependent diabetes mellitus, and expression of this gene is altered in some types of cancer. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

LOC105371754 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.1046-9770A>G		intron_variant		ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5	c.1046-9770A>G		intron_variant		1	NM_000458.4	ENSP00000480291.1
HNF1B	ENST00000621123.4	c.968-9770A>G		intron_variant		1		ENSP00000482711.1
HNF1B	ENST00000613727.4	c.968-9770A>G		intron_variant		1		ENSP00000477524.1
HNF1B	ENST00000614313.4	c.1046-9770A>G		intron_variant		5		ENSP00000482529.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101674 AN: 151740 Hom.: 35340 Cov.: 30

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.670 AC: 101736 AN: 151848 Hom.: 35359 Cov.: 30 AF XY: 0.674 AC XY: 50029 AN XY: 74238

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.703

Alfa AF: 0.727 Hom.: 24588

Bravo AF: 0.655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4794758; hg19: chr17-36080428;