rs2071190

Variant names:

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.527-51T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,571,250 control chromosomes in the GnomAD database, including 47,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4847 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42560 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.613

Publications

29 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=-0.84).

BP6

Variant 12-120993469-T-A is Benign according to our data. Variant chr12-120993469-T-A is described in ClinVar as Benign. ClinVar VariationId is 674357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HNF1A	NM_000545.8 link	c.527-51T>A	intron_variant	Intron 2 of 9	ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2 link	c.527-51T>A	intron_variant	Intron 2 of 9		NP_001293108.2
HNF1A	NM_001406915.1 link	c.527-51T>A	intron_variant	Intron 2 of 8		NP_001393844.1
HNF1A	XM_024449168.2 link	c.527-51T>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.527-51T>A		intron_variant	Intron 2 of 9	1	NM_000545.8	ENSP00000257555.5

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37253

AN:

151920

Hom.:

4829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.241

GnomAD2 exomes

AF:

0.244

AC:

59588

AN:

243864

AF XY:

0.234

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.240

AC:

341185

AN:

1419214

Hom.:

42560

Cov.:

AF XY:

0.236

AC XY:

167246

AN XY:

707948

show subpopulations

African (AFR)

AF:

0.240

AC:

7802

AN:

32530

American (AMR)

AF:

0.392

AC:

17184

AN:

43808

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

3512

AN:

25840

East Asian (EAS)

AF:

0.193

AC:

7633

AN:

39470

South Asian (SAS)

AF:

0.166

AC:

14133

AN:

85054

European-Finnish (FIN)

AF:

0.207

AC:

10855

AN:

52514

Middle Eastern (MID)

AF:

0.107

AC:

539

AN:

5016

European-Non Finnish (NFE)

AF:

0.247

AC:

266148

AN:

1076094

Other (OTH)

AF:

0.227

AC:

13379

AN:

58888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

13463

26927

40390

53854

67317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9126

18252

27378

36504

45630

<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:

0.245

AC:

37314

AN:

152036

Hom.:

4847

Cov.:

AF XY:

0.243

AC XY:

18066

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.248

AC:

10295

AN:

41454

American (AMR)

AF:

0.331

AC:

5051

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

479

AN:

3468

East Asian (EAS)

AF:

0.246

AC:

1273

AN:

5172

South Asian (SAS)

AF:

0.183

AC:

884

AN:

4818

European-Finnish (FIN)

AF:

0.197

AC:

2087

AN:

10576

Middle Eastern (MID)

AF:

0.127

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.242

AC:

16458

AN:

67958

Other (OTH)

AF:

0.237

AC:

499

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1443

2886

4329

5772

7215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.219

Hom.:

700

Bravo

AF:

0.258

Asia WGS

AF:

0.244

AC:

848

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.84

CADD

Benign

0.040

(source)

DANN

Benign

0.61

PhyloP100

-0.61

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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