rs3094509

chr17-37702294-G-A

Variant summary

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

The NM_000458.4(HNF1B):c.1340-1117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,954 control chromosomes in the GnomAD database, including 18,526 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 0.47 (18526 hom., cov: 31)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.1340-1117C>T		intron_variant		ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.1340-1117C>T		intron_variant		1	NM_000458.4
HNF1B	ENST00000613727.4	c.1261+2623C>T		intron_variant		1
HNF1B	ENST00000621123.4	c.1262-1117C>T		intron_variant		1		P1
HNF1B	ENST00000614313.4	c.1340-1117C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71648 AN: 151836 Hom.: 18498 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.472 AC: 71711 AN: 151954 Hom.: 18526 Cov.: 31 AF XY: 0.473 AC XY: 35086 AN XY: 74240

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.455

Alfa AF: 0.411 Hom.: 6469

Bravo AF: 0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	4.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3094509; hg19: chr17-36062299;