chr17-37714971-A-G

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019): 0P and 12B. BA1BP4_Strong

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 cumulative frequency of 0.844 (AC=128,301) in the gnomAD database across 151,976 control chromosomes, including 54,459 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.919. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.75

Publications

103 publications found

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]

HNF1B Gene-Disease associations (from GenCC):

renal cysts and diabetes syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
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

HNF1B links:

LOC105371754 (HGNC:):

LOC105371754 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000458.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.9192 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000458.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF1B	NM_000458.4	MANE Select	c.1046-4308T>C	intron	N/A	NP_000449.1	P35680-1
HNF1B	NM_001411100.1		c.1046-4308T>C	intron	N/A	NP_001398029.1	A0A087WZC2
HNF1B	NM_001165923.4		c.968-4308T>C	intron	N/A	NP_001159395.1	E0YMJ6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF1B	ENST00000617811.5	TSL:1 MANE Select	c.1046-4308T>C	intron	N/A	ENSP00000480291.1	P35680-1
HNF1B	ENST00000621123.4	TSL:1	c.968-4308T>C	intron	N/A	ENSP00000482711.1	P35680-2
HNF1B	ENST00000613727.4	TSL:1	c.968-4308T>C	intron	N/A	ENSP00000477524.1	A0A0C4DGS8

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128204

AN:

151858

Hom.:

54420

Cov.:

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.:

AF XY:

0.844

AC XY:

62706

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.927

AC:

38413

AN:

41438

American (AMR)

AF:

0.813

AC:

12411

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.865

AC:

3005

AN:

3472

East Asian (EAS)

AF:

0.662

AC:

3409

AN:

5152

South Asian (SAS)

AF:

0.850

AC:

4085

AN:

4804

European-Finnish (FIN)

AF:

0.858

AC:

9087

AN:

10590

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.811

AC:

55139

AN:

67950

Other (OTH)

AF:

0.835

AC:

1755

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

992

1983

2975

3966

4958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.825

Hom.:

114939

Bravo

AF:

0.842

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.719

AC:

88325

AN:

122780

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.656

AC:

5874

AN:

8960

Hom.:

1943

ABraOM SABE-WGS-1171

AF:

0.834

AC:

1953

AN:

2342

Hom.:

815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.36

(source)

PhyloP100

-3.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over