17-37687273-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000617811.5(HNF1B):c.*99C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,603,650 control chromosomes in the GnomAD database, including 32,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6842 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25730 hom. )

Consequence

HNF1B
ENST00000617811.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.447

Publications

19 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: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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:

ENSG00000277688 (HGNC:):

ENSG00000277688 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 17-37687273-G-T is Benign according to our data. Variant chr17-37687273-G-T is described in ClinVar as Benign. ClinVar VariationId is 322941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000617811.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HNF1B	NM_000458.4	MANE Select	c.*99C>A	3_prime_UTR	Exon 9 of 9	NP_000449.1
HNF1B	NM_001411100.1		c.*7C>A	3_prime_UTR	Exon 8 of 8	NP_001398029.1
HNF1B	NM_001165923.4		c.*99C>A	3_prime_UTR	Exon 9 of 9	NP_001159395.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HNF1B	ENST00000617811.5	TSL:1 MANE Select	c.*99C>A	3_prime_UTR	Exon 9 of 9	ENSP00000480291.1
HNF1B	ENST00000621123.4	TSL:1	c.*99C>A	3_prime_UTR	Exon 9 of 9	ENSP00000482711.1
HNF1B	ENST00000613727.4	TSL:1	c.*7C>A	3_prime_UTR	Exon 7 of 7	ENSP00000477524.1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39916

AN:

151942

Hom.:

6817

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0985

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.258

GnomAD2 exomes

AF:

0.190

AC:

47177

AN:

248192

AF XY:

0.188

show subpopulations

Gnomad AFR exome

AF:

0.510

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.179

AC:

259225

AN:

1451592

Hom.:

25730

Cov.:

AF XY:

0.180

AC XY:

129772

AN XY:

722564

show subpopulations

African (AFR)

AF:

0.511

AC:

17009

AN:

33282

American (AMR)

AF:

0.132

AC:

5857

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

5894

AN:

26068

East Asian (EAS)

AF:

0.121

AC:

4784

AN:

39604

South Asian (SAS)

AF:

0.207

AC:

17808

AN:

85952

European-Finnish (FIN)

AF:

0.148

AC:

7775

AN:

52666

Middle Eastern (MID)

AF:

0.275

AC:

1580

AN:

5740

European-Non Finnish (NFE)

AF:

0.169

AC:

186547

AN:

1103742

Other (OTH)

AF:

0.199

AC:

11971

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11557

23114

34672

46229

57786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6708

13416

20124

26832

33540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.263

AC:

39998

AN:

152058

Hom.:

6842

Cov.:

AF XY:

0.260

AC XY:

19348

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.495

AC:

20496

AN:

41408

American (AMR)

AF:

0.183

AC:

2790

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

798

AN:

3470

East Asian (EAS)

AF:

0.0987

AC:

511

AN:

5176

South Asian (SAS)

AF:

0.188

AC:

910

AN:

4828

European-Finnish (FIN)

AF:

0.152

AC:

1606

AN:

10590

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12026

AN:

67988

Other (OTH)

AF:

0.260

AC:

549

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1342

2684

4027

5369

6711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.212

Hom.:

971

Bravo

AF:

0.276

Asia WGS

AF:

0.186

AC:

649

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Renal cysts and diabetes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.8

(source)

DANN

Benign

0.82

PhyloP100

-0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over