GeneBe

12-120988742-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000545.8(HNF1A):​c.327-91G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000010 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HNF1A
NM_000545.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.297

Publications

16 publications found
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 Gene-Disease associations (from GenCC):
  • monogenic diabetes
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • type 1 diabetes mellitus 20
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
  • diabetes mellitus, noninsulin-dependent
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • maturity-onset diabetes of the young type 3
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • hyperinsulinism due to HNF1A deficiency
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • maturity-onset diabetes of the young
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • nonpapillary renal cell carcinoma
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNF1ANM_000545.8 linkc.327-91G>C intron_variant Intron 1 of 9 ENST00000257555.11 NP_000536.6 P20823E0YMI7
HNF1ANM_001306179.2 linkc.327-91G>C intron_variant Intron 1 of 9 NP_001293108.2 P20823E0YMI7
HNF1ANM_001406915.1 linkc.327-91G>C intron_variant Intron 1 of 8 NP_001393844.1
HNF1AXM_024449168.2 linkc.327-91G>C intron_variant Intron 1 of 8 XP_024304936.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HNF1AENST00000257555.11 linkc.327-91G>C intron_variant Intron 1 of 9 1 NM_000545.8 ENSP00000257555.5 A0A0A0MQU7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
9.98e-7
AC:
1
AN:
1001930
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
512790
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
24344
American (AMR)
AF:
0.00
AC:
0
AN:
37090
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22810
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35074
South Asian (SAS)
AF:
0.00
AC:
0
AN:
72604
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
44776
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4476
European-Non Finnish (NFE)
AF:
0.00000140
AC:
1
AN:
715496
Other (OTH)
AF:
0.00
AC:
0
AN:
45260
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
4.2
DANN
Benign
0.65
PhyloP100
-0.30

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

Other links and lift over

dbSNP: rs1169293; hg19: chr12-121426545; API