rs3110640

Variant names:

• chr17-37688818-G-A
• rs3110640
• NM_000458.4:c.1654-1426C>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.1654-1426C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,934 control chromosomes in the GnomAD database, including 26,722 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 0.59 (26722 hom., cov: 31)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 10 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

ENSG00000277688 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 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.1654-1426C>T		intron	N/A	NP_000449.1
	HNF1B	NM_001411100.1		c.1535-1426C>T		intron	N/A	NP_001398029.1
	HNF1B	NM_001165923.4		c.1576-1426C>T		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.1654-1426C>T		intron	N/A	ENSP00000480291.1
	HNF1B	ENST00000621123.4	TSL:1	c.1576-1426C>T		intron	N/A	ENSP00000482711.1
	HNF1B	ENST00000613727.4	TSL:1	c.1262-1426C>T		intron	N/A	ENSP00000477524.1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89780 AN: 151814 Hom.: 26681 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.592 AC: 89878 AN: 151934 Hom.: 26722 Cov.: 31 AF XY: 0.593 AC XY: 44043 AN XY: 74260

African (AFR) AF: 0.674 AC: 27938 AN: 41448

American (AMR) AF: 0.623 AC: 9512 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1821 AN: 3464

East Asian (EAS) AF: 0.507 AC: 2606 AN: 5142

South Asian (SAS) AF: 0.571 AC: 2751 AN: 4816

European-Finnish (FIN) AF: 0.565 AC: 5966 AN: 10558

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37388 AN: 67926

Other (OTH) AF: 0.570 AC: 1204 AN: 2114

Alfa AF: 0.561 Hom.: 26819

Bravo AF: 0.599

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.019
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs3110640; hg19: chr17-36048823;