chr12-120978482-G-A

Position:

• chr12-120978482-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000619441.1(HNF1A-AS1):​n.128+2162C>T variant causes a intron, non coding transcript change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNF1A-AS1 ENST00000619441.1 intron, non_coding_transcript
• Clinical Significance: Uncertain significance reviewed by expert panel U:1
• Conservation: PhyloP100: 5.23

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A-AS1	ENST00000619441.1	n.128+2162C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: reviewed by expert panel

Submissions by phenotype

Monogenic diabetes Uncertain:1

Uncertain significance, reviewed by expert panel

curation

ClinGen Monogenic Diabetes Variant Curation Expert Panel

Feb 17, 2022

The c.-287G>A 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). Additionally, the c.-287G>A variant was identified in at least one individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A, and response to low doses of sulfonylurea) (PP4_Moderate; PMID: 23348805). In summary, c.-287G>A 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, PP4_Moderate. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99

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;