rs11649743

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000458.4(HNF1B):​c.1046-4308T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 151,976 control chromosomes in the GnomAD database, including 54,459 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 0.84 ( 54459 hom., cov: 29)

Consequence

HNF1B
NM_000458.4 intron

Scores

1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.75
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HNF1BNM_000458.4 linkuse as main transcriptc.1046-4308T>C intron_variant ENST00000617811.5
LOC105371754XR_001752876.2 linkuse as main transcriptn.684+344A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HNF1BENST00000617811.5 linkuse as main transcriptc.1046-4308T>C intron_variant 1 NM_000458.4 P35680-1
HNF1BENST00000613727.4 linkuse as main transcriptc.968-4308T>C intron_variant 1
HNF1BENST00000621123.4 linkuse as main transcriptc.968-4308T>C intron_variant 1 P1P35680-2
HNF1BENST00000614313.4 linkuse as main transcriptc.1046-4308T>C intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.844
AC:
128204
AN:
151858
Hom.:
54420
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.927
Gnomad AMI
AF:
0.814
Gnomad AMR
AF:
0.813
Gnomad ASJ
AF:
0.865
Gnomad EAS
AF:
0.662
Gnomad SAS
AF:
0.850
Gnomad FIN
AF:
0.858
Gnomad MID
AF:
0.864
Gnomad NFE
AF:
0.811
Gnomad OTH
AF:
0.837
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.844
AC:
128301
AN:
151976
Hom.:
54459
Cov.:
29
AF XY:
0.844
AC XY:
62706
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.927
Gnomad4 AMR
AF:
0.813
Gnomad4 ASJ
AF:
0.865
Gnomad4 EAS
AF:
0.662
Gnomad4 SAS
AF:
0.850
Gnomad4 FIN
AF:
0.858
Gnomad4 NFE
AF:
0.811
Gnomad4 OTH
AF:
0.835
Alfa
AF:
0.816
Hom.:
72088
Bravo
AF:
0.842

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.36

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11649743; hg19: chr17-36074979; API