17-37742044-C-G

Variant names:

• chr17-37742044-C-G
• rs7405696
• NM_000458.4:c.345-2405G>C

Variant summary

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

The NM_000458.4(HNF1B):​c.345-2405G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,168 control chromosomes in the GnomAD database, including 33,616 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 0.65 (33616 hom., cov: 33)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 23 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.345-2405G>C		intron_variant	Intron 1 of 8	ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5	c.345-2405G>C		intron_variant	Intron 1 of 8	1	NM_000458.4	ENSP00000480291.1
HNF1B	ENST00000621123.4	c.345-2405G>C		intron_variant	Intron 1 of 8	1		ENSP00000482711.1
HNF1B	ENST00000613727.4	c.345-2405G>C		intron_variant	Intron 1 of 6	1		ENSP00000477524.1
HNF1B	ENST00000614313.4	c.345-2405G>C		intron_variant	Intron 1 of 7	5		ENSP00000482529.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98106 AN: 152050 Hom.: 33567 Cov.: 33

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.645 AC: 98202 AN: 152168 Hom.: 33616 Cov.: 33 AF XY: 0.636 AC XY: 47294 AN XY: 74392

African (AFR) AF: 0.866 AC: 35987 AN: 41560

American (AMR) AF: 0.562 AC: 8592 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2454 AN: 3466

East Asian (EAS) AF: 0.393 AC: 2026 AN: 5160

South Asian (SAS) AF: 0.624 AC: 3007 AN: 4822

European-Finnish (FIN) AF: 0.420 AC: 4444 AN: 10582

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39413 AN: 67966

Other (OTH) AF: 0.645 AC: 1364 AN: 2114

Alfa AF: 0.597 Hom.: 3344

Bravo AF: 0.661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.23
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs7405696; hg19: chr17-36102035;