rs1169300

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000545.8(HNF1A):c.527-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,215,012 control chromosomes in the GnomAD database, including 66,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6438 hom., cov: 32)

Exomes 𝑓: 0.33 ( 60252 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0730

Publications

45 publications found

Variant links:

Genes affected

HNF1A (HGNC:11621): (HNF1 homeobox A) The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

HNF1A Gene-Disease associations (from GenCC):

monogenic diabetes
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
type 1 diabetes mellitus 20
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
diabetes mellitus, noninsulin-dependent
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
maturity-onset diabetes of the young type 3
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hyperinsulinism due to HNF1A deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
maturity-onset diabetes of the young
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
nonpapillary renal cell carcinoma
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

HNF1A 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=-0.96).

BP6

Variant 12-120993422-G-A is Benign according to our data. Variant chr12-120993422-G-A is described in ClinVar as Benign. ClinVar VariationId is 676874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HNF1A	NM_000545.8 link	c.527-98G>A	intron_variant	Intron 2 of 9	ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2 link	c.527-98G>A	intron_variant	Intron 2 of 9		NP_001293108.2
HNF1A	NM_001406915.1 link	c.527-98G>A	intron_variant	Intron 2 of 8		NP_001393844.1
HNF1A	XM_024449168.2 link	c.527-98G>A	intron_variant	Intron 2 of 8		XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11 link	c.527-98G>A		intron_variant	Intron 2 of 9	1	NM_000545.8	ENSP00000257555.5

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41605

AN:

151968

Hom.:

6435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.332

AC:

352809

AN:

1062926

Hom.:

60252

AF XY:

0.335

AC XY:

181170

AN XY:

541266

show subpopulations

African (AFR)

AF:

0.131

AC:

3318

AN:

25292

American (AMR)

AF:

0.374

AC:

13863

AN:

37068

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

11082

AN:

23388

East Asian (EAS)

AF:

0.528

AC:

19252

AN:

36496

South Asian (SAS)

AF:

0.416

AC:

31048

AN:

74560

European-Finnish (FIN)

AF:

0.309

AC:

14283

AN:

46284

Middle Eastern (MID)

AF:

0.469

AC:

1662

AN:

3544

European-Non Finnish (NFE)

AF:

0.315

AC:

242206

AN:

768992

Other (OTH)

AF:

0.340

AC:

16095

AN:

47302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

12753

25506

38259

51012

63765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7040

14080

21120

28160

35200

<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:

0.274

AC:

41609

AN:

152086

Hom.:

6438

Cov.:

AF XY:

0.281

AC XY:

20893

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.131

AC:

5441

AN:

41510

American (AMR)

AF:

0.344

AC:

5264

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

1594

AN:

3472

East Asian (EAS)

AF:

0.486

AC:

2510

AN:

5164

South Asian (SAS)

AF:

0.403

AC:

1943

AN:

4824

European-Finnish (FIN)

AF:

0.321

AC:

3390

AN:

10556

Middle Eastern (MID)

AF:

0.503

AC:

148

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20334

AN:

67962

Other (OTH)

AF:

0.314

AC:

662

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1534

3068

4603

6137

7671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.297

Hom.:

23357

Bravo

AF:

0.269

Asia WGS

AF:

0.421

AC:

1461

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 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.9

(source)

DANN

Benign

0.48

PhyloP100

0.073

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