rs8068014

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001411100.1(HNF1B):c.1602T>G(p.Phe534Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,614,022 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 177 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 195 hom. )

Consequence

HNF1B
NM_001411100.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.69

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018926263).

BP6

Variant 17-37687325-A-C is Benign according to our data. Variant chr17-37687325-A-C is described in ClinVar as [Benign]. Clinvar id is 322943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.092 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4 link	c.*47T>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000617811.5	NP_000449.1	P35680-1Q6FHW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HNF1B	ENST00000613727.4 link	c.1329T>G	p.Phe443Leu	missense_variant	Exon 7 of 7	1		ENSP00000477524.1	A0A0C4DGS8
HNF1B	ENST00000617811 link	c.*47T>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_000458.4	ENSP00000480291.1	P35680-1
HNF1B	ENST00000621123 link	c.*47T>G		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000482711.1	P35680-2
HNF1B	ENST00000614313.4 link	c.1602T>G	p.Phe534Leu	missense_variant	Exon 8 of 8	5		ENSP00000482529.1	A0A087WZC2

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4090

AN:

152142

Hom.:

177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0946

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00705

AC:

1773

AN:

251314

Hom.:

AF XY:

0.00518

AC XY:

704

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0977

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00273

AC:

3988

AN:

1461762

Hom.:

195

Cov.:

AF XY:

0.00242

AC XY:

1761

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0988

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000127

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.0269

AC:

4092

AN:

152260

Hom.:

177

Cov.:

AF XY:

0.0257

AC XY:

1915

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0944

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0298

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0919

AC:

405

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00872

AC:

1059

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Renal cysts and diabetes syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Monogenic diabetes

Benign:1

Oct 11, 2016

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG Criteria: PP3, BS1 (ExAC AFR), BS2 (ExAC, type2diabetesgenetics.org), BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;T

Eigen

Benign

0.10

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.96

MetaRNN

Benign

0.0019

T;T

MetaSVM

Uncertain

-0.097

Sift4G

Benign

0.64

T;T

Vest4

0.25

MVP

0.76

ClinPred

0.015

GERP RS

4.9

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over