Variant 12-120978302-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The ENST00000433033.3(HNF1A-AS1):n.134+1312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 152,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Consequence

HNF1A-AS1
ENST00000433033.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -2.42

Variant links:

Genes affected

HNF1A-AS1 (HGNC:26785): (HNF1A antisense RNA 1)

HNF1A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-120978302-C-T is Benign according to our data. Variant chr12-120978302-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 449034.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL
HNF1A-AS1	ENST00000433033.3 link	n.134+1312G>A	intron_variant	3
HNF1A-AS1	ENST00000535301.2 link	n.322+2342G>A	intron_variant	4
HNF1A-AS1	ENST00000537361.1 link	n.263+2342G>A	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.000270

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.000893

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000310

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 30, 2017

The c.-467 C>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is observed in 4/8716 (0.046%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). This variant occurs at a position that is not conserved. Other regulatory variants, including nearby c.-462G>A, have been reported in the Human Gene Mutation Database in association with HNF1A-associated disorders (Stenson et al., 2014). In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -

HNF1A-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 05, 2024

The HNF1A c.-467C>T variant is located in the 5' untranslated region. To our knowledge, this variant has not been reported in the literature. Of note, other pre-coding variants have been reported in patients with maturity onset diabetes of the young (MODY) or type 2 diabetes (see for example at Colclough et al. 2013. PubMed ID: 23348805; Cox et al. 1999. PubMed ID: 10027593). This variant is reported in 0.046% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

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 rs1039479235 with MODY3. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.21

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

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