12-120978739-C-T

Variant names:

• chr12-120978739-C-T
• rs759730121
• NM_000545.8:c.-30C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000545.8(HNF1A):​c.-30C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,454,484 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: HNF1A NM_000545.8 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.82
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BS2: High AC in GnomAdExome4 at 9 AD,Unknown gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1A	NM_000545.8	MANE Select	c.-30C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_000536.6
	HNF1A	NM_000545.8	MANE Select	c.-30C>T		5_prime_UTR	Exon 1 of 10	NP_000536.6
	HNF1A	NM_001306179.2		c.-30C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001293108.2	F5H0K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1A	ENST00000257555.11	TSL:1 MANE Select	c.-30C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000257555.5	P20823-1
	HNF1A	ENST00000257555.11	TSL:1 MANE Select	c.-30C>T		5_prime_UTR	Exon 1 of 10	ENSP00000257555.5	P20823-1
	HNF1A	ENST00000538646.5	TSL:1	n.-30C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000443964.1	P20823-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 241088 AF XY: 0.00000755

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000474

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1454484 Hom.: 0 Cov.: 29 AF XY: 0.00000691 AC XY: 5 AN XY: 723908

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.0000671 AC: 3 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86064

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1106884

Other (OTH) AF: 0.0000166 AC: 1 AN: 60162

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.4
DANN	Benign	0.89
PhyloP100		-2.8
PromoterAI		0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs759730121; hg19: chr12-121416542;