dbSNP rs1016990: HNF1B:c.1045+2671C>G (chr17-37728924-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000458.4(HNF1B):c.1045+2671C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 154,426 control chromosomes in the GnomAD database, including 6,568 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 0.27 ( 6452 hom., cov: 31)

Exomes 𝑓: 0.31 ( 116 hom. )

Consequence

HNF1B
NM_000458.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.959

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4 link	c.1045+2671C>G		intron_variant	Intron 4 of 8	ENST00000617811.5	NP_000449.1	P35680-1Q6FHW6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5 link	c.1045+2671C>G		intron_variant	Intron 4 of 8	1	NM_000458.4	ENSP00000480291.1		P35680-1

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41308

AN:

152032

Hom.:

6448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.300

GnomAD4 exome

AF:

0.311

AC:

708

AN:

2274

Hom.:

116

Cov.:

AF XY:

0.286

AC XY:

360

AN XY:

1260

show subpopulations

African (AFR)

AF:

0.271

AC:

AN:

American (AMR)

AF:

0.188

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

AN:

East Asian (EAS)

AF:

0.313

AC:

AN:

252

South Asian (SAS)

AF:

0.200

AC:

AN:

European-Finnish (FIN)

AF:

0.259

AC:

115

AN:

444

Middle Eastern (MID)

AF:

0.400

AC:

AN:

European-Non Finnish (NFE)

AF:

0.334

AC:

450

AN:

1346

Other (OTH)

AF:

0.208

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.272

AC:

41314

AN:

152152

Hom.:

6452

Cov.:

AF XY:

0.268

AC XY:

19959

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.122

AC:

5060

AN:

41518

American (AMR)

AF:

0.247

AC:

3778

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1419

AN:

3472

East Asian (EAS)

AF:

0.370

AC:

1912

AN:

5170

South Asian (SAS)

AF:

0.273

AC:

1315

AN:

4824

European-Finnish (FIN)

AF:

0.256

AC:

2706

AN:

10590

Middle Eastern (MID)

AF:

0.349

AC:

102

AN:

292

European-Non Finnish (NFE)

AF:

0.352

AC:

23961

AN:

67980

Other (OTH)

AF:

0.297

AC:

627

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1504

3008

4511

6015

7519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.180

Hom.:

392

Bravo

AF:

0.267

Asia WGS

AF:

0.290

AC:

1010

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.5

(source)

DANN

Benign

0.58

PhyloP100

0.96

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

Computational scores

Splicing

Publications

Other links and lift over