Variant 12-120997784-G-T 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.1501+119G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,098,004 control chromosomes in the GnomAD database, including 71,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8634 hom., cov: 32)

Exomes 𝑓: 0.35 ( 63048 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.113

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=-0.86).

BP6

Variant 12-120997784-G-T is Benign according to our data. Variant chr12-120997784-G-T is described in ClinVar as [Benign]. Clinvar id is 676877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-120997784-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HNF1A	NM_000545.8 linkuse as main transcript	c.1501+119G>T	intron_variant	ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2 linkuse as main transcript	c.1501+119G>T	intron_variant		NP_001293108.2
HNF1A	NM_001406915.1 linkuse as main transcript	c.1309+1042G>T	intron_variant		NP_001393844.1
HNF1A	XM_024449168.2 linkuse as main transcript	c.1501+119G>T	intron_variant		XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11 linkuse as main transcript	c.1501+119G>T		intron_variant		1	NM_000545.8	ENSP00000257555	P4

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48271

AN:

151952

Hom.:

8631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.488

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.366

GnomAD3 exomes

AF:

0.401

AC:

60157

AN:

150168

Hom.:

12655

AF XY:

0.412

AC XY:

33118

AN XY:

80318

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.487

Gnomad SAS exome

AF:

0.519

Gnomad FIN exome

AF:

0.377

Gnomad NFE exome

AF:

0.363

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.355

AC:

335349

AN:

945932

Hom.:

63048

Cov.:

AF XY:

0.364

AC XY:

175919

AN XY:

483838

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.503

Gnomad4 EAS exome

AF:

0.522

Gnomad4 SAS exome

AF:

0.511

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.317

AC:

48273

AN:

152072

Hom.:

8634

Cov.:

AF XY:

0.327

AC XY:

24317

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.503

Gnomad4 EAS

AF:

0.488

Gnomad4 SAS

AF:

0.512

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.358

Hom.:

22220

Bravo

AF:

0.308

Asia WGS

AF:

0.477

AC:

1654

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
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

-0.86

CADD

Benign

1.8

DANN

Benign

0.57

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