12-120978369-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The ENST00000433033.3(HNF1A-AS1):​n.134+1245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 152,312 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 31)

Consequence

HNF1A-AS1
ENST00000433033.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.755
Variant links:
Genes affected
HNF1A-AS1 (HGNC:26785): (HNF1A antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 12-120978369-C-T is Benign according to our data. Variant chr12-120978369-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 675908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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-AS1ENST00000433033.3 linkn.134+1245G>A intron_variant Intron 1 of 3 3
HNF1A-AS1ENST00000535301.2 linkn.322+2275G>A intron_variant Intron 1 of 1 4
HNF1A-AS1ENST00000537361.1 linkn.263+2275G>A intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00185
AC:
282
AN:
152194
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00637
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000958
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00183
AC:
279
AN:
152312
Hom.:
0
Cov.:
31
AF XY:
0.00187
AC XY:
139
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00628
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.00146
Hom.:
0
Bravo
AF:
0.00224

ClinVar

Significance: Likely 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
-
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: research

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 rs77774709 with MODY3. -

not provided Benign:1
Mar 20, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
-0.74
CADD
Benign
12
DANN
Benign
0.88

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.

Other links and lift over

dbSNP: rs77774709; hg19: chr12-121416172; API