chr17-37743574-A-G

Position:

• chr17-37743574-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000458.4(HNF1B):​c.344+967T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,220 control chromosomes in the GnomAD database, including 14,295 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 0.43 (14295 hom., cov: 34)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522

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 (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.344+967T>C		intron_variant		ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.344+967T>C		intron_variant		1	NM_000458.4
HNF1B	ENST00000613727.4	c.344+967T>C		intron_variant		1
HNF1B	ENST00000621123.4	c.344+967T>C		intron_variant		1		P1
HNF1B	ENST00000614313.4	c.344+967T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64895 AN: 152102 Hom.: 14295 Cov.: 34

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.426 AC: 64908 AN: 152220 Hom.: 14295 Cov.: 34 AF XY: 0.419 AC XY: 31150 AN XY: 74414

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.462

Alfa AF: 0.425 Hom.: 5802

Bravo AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.5

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11263763; hg19: chr17-36103565;