12-120982457-A-G

Position:

• chr12-120982457-A-G

Variant summary

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

The NM_000545.8(HNF1A):​c.326+3363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 150,652 control chromosomes in the GnomAD database, including 25,345 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 0.58 (25345 hom., cov: 29)
• Consequence: HNF1A NM_000545.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1A	NM_000545.8	c.326+3363A>G		intron_variant		ENST00000257555.11
HNF1A	NM_001306179.2	c.326+3363A>G		intron_variant
HNF1A	NM_001406915.1	c.326+3363A>G		intron_variant
HNF1A	XM_024449168.2	c.326+3363A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11	c.326+3363A>G		intron_variant		1	NM_000545.8	P4

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87308 AN: 150534 Hom.: 25301 Cov.: 29

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.580 AC: 87409 AN: 150652 Hom.: 25345 Cov.: 29 AF XY: 0.573 AC XY: 42201 AN XY: 73658

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.561

Alfa AF: 0.584 Hom.: 25104

Bravo AF: 0.580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.18

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: rs7979473; hg19: chr12-121420260;