12-120978482-GTC-G

Variant names:

• chr12-120978482-GTC-G
• ENST00000433033.3:n.134+1130_134+1131delGA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000433033.3(HNF1A-AS1):​n.134+1130_134+1131delGA variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HNF1A-AS1 ENST00000433033.3 intron
• Clinical Significance: Uncertain significance reviewed by expert panel U:1
• Conservation: PhyloP100: 4.02

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1A-AS1	ENST00000433033.3	n.134+1130_134+1131delGA		intron_variant	Intron 1 of 3	3
HNF1A-AS1	ENST00000535301.2	n.322+2160_322+2161delGA		intron_variant	Intron 1 of 1	4
HNF1A-AS1	ENST00000537361.1	n.263+2160_263+2161delGA		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: reviewed by expert panel

Submissions by phenotype

Monogenic diabetes Uncertain:1

Apr 12, 2022

ClinGen Monogenic Diabetes Variant Curation Expert Panel

Significance: Uncertain significance

Review Status: reviewed by expert panel

Collection Method: curation

The c.-286_-285del variant in the HNF1 homeobox A gene, HNF1A, is located in the promoter of NM_000545.8. This region is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting) and is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result nearly 50%); however, HNF4A was not tested (internal lab contributors), and therefore PP4 was not applied. In summary, c.-286_-285del meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): PM1_supporting, PM2_Supporting. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-121416285;