rs718961

Variant names:

• chr17-37717101-A-G
• rs718961
• NM_000458.4:c.1046-6438T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-37717101-A-G
• chr17-37717101-A-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.1046-6438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,112 control chromosomes in the GnomAD database, including 51,425 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 0.82 (51425 hom., cov: 31)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 13 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

LOC105371754 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 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.1046-6438T>C		intron	N/A	NP_000449.1	P35680-1
	HNF1B	NM_001411100.1		c.1046-6438T>C		intron	N/A	NP_001398029.1	A0A087WZC2
	HNF1B	NM_001165923.4		c.968-6438T>C		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.1046-6438T>C		intron	N/A	ENSP00000480291.1	P35680-1
	HNF1B	ENST00000621123.4	TSL:1	c.968-6438T>C		intron	N/A	ENSP00000482711.1	P35680-2
	HNF1B	ENST00000613727.4	TSL:1	c.968-6438T>C		intron	N/A	ENSP00000477524.1	A0A0C4DGS8

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124360 AN: 151994 Hom.: 51383 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.818 AC: 124463 AN: 152112 Hom.: 51425 Cov.: 31 AF XY: 0.814 AC XY: 60561 AN XY: 74354

African (AFR) AF: 0.940 AC: 39018 AN: 41518

American (AMR) AF: 0.793 AC: 12121 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2547 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3451 AN: 5166

South Asian (SAS) AF: 0.798 AC: 3842 AN: 4812

European-Finnish (FIN) AF: 0.768 AC: 8111 AN: 10564

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.777 AC: 52807 AN: 67974

Other (OTH) AF: 0.791 AC: 1669 AN: 2110

Alfa AF: 0.783 Hom.: 29902

Bravo AF: 0.823

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
PhyloP100		0.018

Splicing

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

Other links and lift over

dbSNP: rs718961; hg19: chr17-36077099;