Genetic Variant HNF1A:c.-123G>T (chr12-120978646-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000545.8(HNF1A):c.-123G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 780,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene HNF1A is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

HNF1A
NM_000545.8 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.26

Publications

0 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 links:

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

HNF1A-AS1 links:

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new If you want to explore the variant's impact on the transcript NM_000545.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for HNF1A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000545.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF1A	NM_000545.8	MANE Select	c.-123G>T	5_prime_UTR	Exon 1 of 10	NP_000536.6
HNF1A	NM_001306179.2		c.-123G>T	5_prime_UTR	Exon 1 of 10	NP_001293108.2	F5H0K0
HNF1A	NM_001406915.1		c.-123G>T	5_prime_UTR	Exon 1 of 9	NP_001393844.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF1A	ENST00000257555.11	TSL:1 MANE Select	c.-123G>T	5_prime_UTR	Exon 1 of 10	ENSP00000257555.5	P20823-1
HNF1A	ENST00000560968.6	TSL:1	n.-123G>T	non_coding_transcript_exon	Exon 1 of 10	ENSP00000453965.2	E0YMI8
HNF1A	ENST00000560968.6	TSL:1	n.-123G>T	5_prime_UTR	Exon 1 of 10	ENSP00000453965.2	E0YMI8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000128

AC:

AN:

780536

Hom.:

Cov.:

AF XY:

0.00000242

AC XY:

AN XY:

412988

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20786

American (AMR)

AF:

0.00

AC:

AN:

40852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21650

East Asian (EAS)

AF:

0.00

AC:

AN:

35486

South Asian (SAS)

AF:

0.00

AC:

AN:

70110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3846

European-Non Finnish (NFE)

AF:

0.00000195

AC:

AN:

511848

Other (OTH)

AF:

0.00

AC:

AN:

38190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

3.3

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over