rs757210

chr17-37736525-C-Gchr17-37736525-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000458.4(HNF1B):c.545-2704G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 152,054 control chromosomes in the GnomAD database, including 43 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 0.018 (43 hom., cov: 31)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.047).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0178 (2706/152054) while in subpopulation NFE AF= 0.0241 (1638/67982). AF 95% confidence interval is 0.0231. There are 43 homozygotes in gnomad4. There are 1331 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2706 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.545-2704G>C		intron_variant		ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.545-2704G>C		intron_variant		1	NM_000458.4
HNF1B	ENST00000613727.4	c.545-2782G>C		intron_variant		1
HNF1B	ENST00000621123.4	c.545-2782G>C		intron_variant		1		P1
HNF1B	ENST00000614313.4	c.545-2704G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2706 AN: 151936 Hom.: 43 Cov.: 31

Gnomad AFR AF: 0.00462

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0173

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

GnomAD4 genome AF: 0.0178 AC: 2706 AN: 152054 Hom.: 43 Cov.: 31 AF XY: 0.0179 AC XY: 1331 AN XY: 74344

Gnomad4 AFR AF: 0.00461

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.000533 Hom.: 15577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.047

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

Publications

LitVar

Other links and lift over

dbSNP: rs757210; hg19: -;