Variant 12-120988791-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000545.8(HNF1A):c.327-42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,595,190 control chromosomes in the GnomAD database, including 86,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7146 hom., cov: 33)

Exomes 𝑓: 0.33 ( 78905 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.273

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-120988791-G-A is Benign according to our data. Variant chr12-120988791-G-A is described in ClinVar as [Benign]. Clinvar id is 673535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-120988791-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HNF1A	NM_000545.8 linkuse as main transcript	c.327-42G>A	intron_variant	ENST00000257555.11
HNF1A	NM_001306179.2 linkuse as main transcript	c.327-42G>A	intron_variant
HNF1A	NM_001406915.1 linkuse as main transcript	c.327-42G>A	intron_variant
HNF1A	XM_024449168.2 linkuse as main transcript	c.327-42G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11 linkuse as main transcript	c.327-42G>A		intron_variant		1	NM_000545.8	P4

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44742

AN:

152044

Hom.:

7145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.313

GnomAD3 exomes

AF:

0.348

AC:

84443

AN:

242538

Hom.:

15053

AF XY:

0.353

AC XY:

46269

AN XY:

131146

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.406

Gnomad SAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.376

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.353

GnomAD4 exome

AF:

0.327

AC:

471715

AN:

1443028

Hom.:

78905

Cov.:

AF XY:

0.330

AC XY:

237293

AN XY:

718632

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.452

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.367

Gnomad4 NFE exome

AF:

0.313

Gnomad4 OTH exome

AF:

0.336

GnomAD4 genome

AF:

0.294

AC:

44744

AN:

152162

Hom.:

7146

Cov.:

AF XY:

0.302

AC XY:

22486

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.355

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.318

Hom.:

2148

Bravo

AF:

0.284

Asia WGS

AF:

0.399

AC:

1385

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Maturity onset diabetes mellitus in young

Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs1169294 with MODY3. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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

-0.83

CADD

Benign

0.25

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over