dbSNP rs3744763: HNF1B:c.1045+701T>C (chr17-37730894-A-G) – 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+701T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 155,150 control chromosomes in the GnomAD database, including 9,071 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 0.31 ( 8866 hom., cov: 32)

Exomes 𝑓: 0.33 ( 205 hom. )

Consequence

HNF1B
NM_000458.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.937

Publications

18 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4 link	c.1045+701T>C		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+701T>C		intron_variant	Intron 4 of 8	1	NM_000458.4	ENSP00000480291.1		P35680-1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47285

AN:

151964

Hom.:

8865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.344

GnomAD4 exome

AF:

0.334

AC:

1024

AN:

3068

Hom.:

205

Cov.:

AF XY:

0.341

AC XY:

530

AN XY:

1554

show subpopulations

African (AFR)

AF:

0.0625

AC:

AN:

American (AMR)

AF:

0.232

AC:

179

AN:

770

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.345

AC:

AN:

142

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.370

AC:

723

AN:

1952

Other (OTH)

AF:

0.361

AC:

AN:

108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.311

AC:

47271

AN:

152082

Hom.:

8866

Cov.:

AF XY:

0.309

AC XY:

22954

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.104

AC:

4322

AN:

41524

American (AMR)

AF:

0.286

AC:

4363

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1530

AN:

3466

East Asian (EAS)

AF:

0.545

AC:

2807

AN:

5150

South Asian (SAS)

AF:

0.400

AC:

1927

AN:

4814

European-Finnish (FIN)

AF:

0.309

AC:

3263

AN:

10576

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.409

AC:

27790

AN:

67970

Other (OTH)

AF:

0.340

AC:

716

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1541

3082

4624

6165

7706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.388

Hom.:

27027

Bravo

AF:

0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.42

(source)

PhyloP100

-0.94

Splicing

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