rs1016990

Variant names:

• chr17-37728924-G-C
• rs1016990
• NM_000458.4:c.1045+2671C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-37728924-G-C
• chr17-37728924-G-T

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+2671C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 154,426 control chromosomes in the GnomAD database, including 6,568 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 0.27 (6452 hom., cov: 31)
  • Exomes 𝑓: 0.31 (116 hom.)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959
• Publications: 9 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet, ClinGen
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	NM_000458.4	MANE Select	c.1045+2671C>G		intron	N/A	NP_000449.1	P35680-1
	HNF1B	NM_001411100.1		c.1045+2671C>G		intron	N/A	NP_001398029.1	A0A087WZC2
	HNF1B	NM_001165923.4		c.967+2671C>G		intron	N/A	NP_001159395.1	E0YMJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	ENST00000617811.5	TSL:1 MANE Select	c.1045+2671C>G		intron	N/A	ENSP00000480291.1	P35680-1
	HNF1B	ENST00000621123.4	TSL:1	c.967+2671C>G		intron	N/A	ENSP00000482711.1	P35680-2
	HNF1B	ENST00000613727.4	TSL:1	c.967+2671C>G		intron	N/A	ENSP00000477524.1	A0A0C4DGS8

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41308 AN: 152032 Hom.: 6448 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.311 AC: 708 AN: 2274 Hom.: 116 Cov.: 0 AF XY: 0.286 AC XY: 360 AN XY: 1260

African (AFR) AF: 0.271 AC: 13 AN: 48

American (AMR) AF: 0.188 AC: 6 AN: 32

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 24 AN: 60

East Asian (EAS) AF: 0.313 AC: 79 AN: 252

South Asian (SAS) AF: 0.200 AC: 2 AN: 10

European-Finnish (FIN) AF: 0.259 AC: 115 AN: 444

Middle Eastern (MID) AF: 0.400 AC: 4 AN: 10

European-Non Finnish (NFE) AF: 0.334 AC: 450 AN: 1346

Other (OTH) AF: 0.208 AC: 15 AN: 72

GnomAD4 genome AF: 0.272 AC: 41314 AN: 152152 Hom.: 6452 Cov.: 31 AF XY: 0.268 AC XY: 19959 AN XY: 74384

African (AFR) AF: 0.122 AC: 5060 AN: 41518

American (AMR) AF: 0.247 AC: 3778 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1419 AN: 3472

East Asian (EAS) AF: 0.370 AC: 1912 AN: 5170

South Asian (SAS) AF: 0.273 AC: 1315 AN: 4824

European-Finnish (FIN) AF: 0.256 AC: 2706 AN: 10590

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.352 AC: 23961 AN: 67980

Other (OTH) AF: 0.297 AC: 627 AN: 2110

Alfa AF: 0.180 Hom.: 392

Bravo AF: 0.267

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.5
DANN	Benign	0.58
PhyloP100		0.96
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: rs1016990; hg19: chr17-36088915;