chr17-37692682-G-A

Position:

• chr17-37692682-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.1654-5290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,204 control chromosomes in the GnomAD database, including 2,521 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 0.17 (2521 hom., cov: 32)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.1654-5290C>T		intron_variant		ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.1654-5290C>T		intron_variant		1	NM_000458.4
HNF1B	ENST00000613727.4	c.1262-5290C>T		intron_variant		1
HNF1B	ENST00000621123.4	c.1576-5290C>T		intron_variant		1		P1
HNF1B	ENST00000614313.4	c.1535-5290C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25194 AN: 152086 Hom.: 2518 Cov.: 32

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.166 AC: 25197 AN: 152204 Hom.: 2521 Cov.: 32 AF XY: 0.168 AC XY: 12491 AN XY: 74412

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.183

Alfa AF: 0.197 Hom.: 3455

Bravo AF: 0.159

Asia WGS AF: 0.259 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.70

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: rs11868513; hg19: chr17-36052692;