chr17-37704890-A-G

Variant names:

Variant summary

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

The NM_000458.4(HNF1B):c.1339+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,612,856 control chromosomes in the GnomAD database, including 12,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 724 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11357 hom. )

Consequence

HNF1B
NM_000458.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.629

Publications

9 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:

LOC124903989 (HGNC:):

LOC124903989 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=-0.87).

BP6

Variant 17-37704890-A-G is Benign according to our data. Variant chr17-37704890-A-G is described in ClinVar as Benign. ClinVar VariationId is 1279728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4 link	c.1339+27T>C		intron_variant	Intron 6 of 8	ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
HNF1B	ENST00000617811.5 link	c.1339+27T>C	intron_variant	Intron 6 of 8	1	NM_000458.4	ENSP00000480291.1
HNF1B	ENST00000621123.4 link	c.1261+27T>C	intron_variant	Intron 6 of 8	1		ENSP00000482711.1
HNF1B	ENST00000613727.4 link	c.1261+27T>C	intron_variant	Intron 6 of 6	1		ENSP00000477524.1
HNF1B	ENST00000614313.4 link	c.1339+27T>C	intron_variant	Intron 6 of 7	5		ENSP00000482529.1

Frequencies

GnomAD3 genomes

AF:

0.0872

AC:

13260

AN:

152080

Hom.:

724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0303

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0697

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0727

Gnomad FIN

AF:

0.0854

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.0975

GnomAD2 exomes

AF:

0.0919

AC:

23102

AN:

251464

AF XY:

0.0965

show subpopulations

Gnomad AFR exome

AF:

0.0282

Gnomad AMR exome

AF:

0.0492

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0813

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.119

AC:

173695

AN:

1460658

Hom.:

11357

Cov.:

AF XY:

0.119

AC XY:

86253

AN XY:

726728

show subpopulations

African (AFR)

AF:

0.0276

AC:

924

AN:

33476

American (AMR)

AF:

0.0523

AC:

2341

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

3847

AN:

26124

East Asian (EAS)

AF:

0.000403

AC:

AN:

39692

South Asian (SAS)

AF:

0.0778

AC:

6713

AN:

86248

European-Finnish (FIN)

AF:

0.0794

AC:

4238

AN:

53406

Middle Eastern (MID)

AF:

0.114

AC:

659

AN:

5762

European-Non Finnish (NFE)

AF:

0.133

AC:

148176

AN:

1110878

Other (OTH)

AF:

0.112

AC:

6781

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

7060

14121

21181

28242

35302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5272

10544

15816

21088

26360

<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:

0.0871

AC:

13253

AN:

152198

Hom.:

724

Cov.:

AF XY:

0.0842

AC XY:

6263

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0302

AC:

1254

AN:

41520

American (AMR)

AF:

0.0697

AC:

1066

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

554

AN:

3468

East Asian (EAS)

AF:

0.00154

AC:

AN:

5188

South Asian (SAS)

AF:

0.0723

AC:

349

AN:

4824

European-Finnish (FIN)

AF:

0.0854

AC:

905

AN:

10592

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.130

AC:

8809

AN:

67996

Other (OTH)

AF:

0.0960

AC:

203

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

632

1264

1895

2527

3159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.116

Hom.:

882

Bravo

AF:

0.0829

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Jun 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.11

(source)

DANN

Benign

0.77

PhyloP100

-0.63

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over