rs718961

chr17-37717101-A-Gchr17-37717101-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105371754 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.1046-6438T>C		intron_variant		ENST00000617811.5
LOC105371754	XR_001752876.2	n.685-299A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.1046-6438T>C		intron_variant		1	NM_000458.4
HNF1B	ENST00000613727.4	c.968-6438T>C		intron_variant		1
HNF1B	ENST00000621123.4	c.968-6438T>C		intron_variant		1		P1
HNF1B	ENST00000614313.4	c.1046-6438T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.791

Alfa AF: 0.784 Hom.: 13053

Bravo AF: 0.823

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs718961; hg19: chr17-36077099;