12-120998573-A-C

Position:

• chr12-120998573-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000545.8(HNF1A):​c.1502-695A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,900 control chromosomes in the GnomAD database, including 16,580 homozygotes. 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: 𝑓 0.45 (16580 hom., cov: 32)
• Consequence: HNF1A NM_000545.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1A	NM_000545.8	c.1502-695A>C		intron_variant		ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2	c.1502-695A>C		intron_variant			NP_001293108.2
HNF1A	NM_001406915.1	c.1310-695A>C		intron_variant			NP_001393844.1
HNF1A	XM_024449168.2	c.1502-695A>C		intron_variant			XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11	c.1502-695A>C		intron_variant		1	NM_000545.8	ENSP00000257555.5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68833 AN: 151782 Hom.: 16570 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.453 AC: 68864 AN: 151900 Hom.: 16580 Cov.: 32 AF XY: 0.462 AC XY: 34333 AN XY: 74248

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.490

Alfa AF: 0.483 Hom.: 29954

Bravo AF: 0.440

Asia WGS AF: 0.680 AC: 2361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.046
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.96

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

LitVar

Other links and lift over

dbSNP: rs1169303; hg19: chr12-121436376;