17-37727883-G-C

Variant names:

• chr17-37727883-G-C
• rs3786127
• NM_000458.4:c.1045+3712C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000458.4(HNF1B):​c.1045+3712C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,114 control chromosomes in the GnomAD database, including 1,438 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 0.12 (1438 hom., cov: 31)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 5 publications found

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]

HNF1B Gene-Disease associations (from GenCC):

• renal cysts and diabetes syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• diabetes mellitus, noninsulin-dependent

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• permanent neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• transient neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• medullary sponge kidney

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal dysplasia, bilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal dysplasia, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal hypomagnesemia 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• unilateral multicystic dysplastic kidney

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000458.4. 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
	HNF1B	NM_000458.4	MANE Select	c.1045+3712C>G		intron	N/A	NP_000449.1
	HNF1B	NM_001411100.1		c.1045+3712C>G		intron	N/A	NP_001398029.1
	HNF1B	NM_001165923.4		c.967+3712C>G		intron	N/A	NP_001159395.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	ENST00000617811.5	TSL:1 MANE Select	c.1045+3712C>G		intron	N/A	ENSP00000480291.1
	HNF1B	ENST00000621123.4	TSL:1	c.967+3712C>G		intron	N/A	ENSP00000482711.1
	HNF1B	ENST00000613727.4	TSL:1	c.967+3712C>G		intron	N/A	ENSP00000477524.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18739 AN: 151996 Hom.: 1439 Cov.: 31

Gnomad AFR AF: 0.0425

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.123 AC: 18730 AN: 152114 Hom.: 1438 Cov.: 31 AF XY: 0.125 AC XY: 9330 AN XY: 74354

African (AFR) AF: 0.0424 AC: 1758 AN: 41506

American (AMR) AF: 0.105 AC: 1608 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3468

East Asian (EAS) AF: 0.167 AC: 862 AN: 5176

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4812

European-Finnish (FIN) AF: 0.195 AC: 2062 AN: 10572

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10311 AN: 67970

Other (OTH) AF: 0.134 AC: 283 AN: 2110

Alfa AF: 0.0462 Hom.: 54

Bravo AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-0.15
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: rs3786127; hg19: chr17-36087874;