rs1169303

Variant names:

• chr12-120998573-A-C
• rs1169303
• NM_000545.8:c.1502-695A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-120998573-A-C
• chr12-120998573-A-G
• chr12-120998573-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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 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)

ACMG classification

Our verdict: Benign. The variant received -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.

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.1502-695A>C		intron	N/A	NP_000536.6
	HNF1A	NM_001306179.2		c.1502-695A>C		intron	N/A	NP_001293108.2	F5H0K0
	HNF1A	NM_001406915.1		c.1310-695A>C		intron	N/A	NP_001393844.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1A	ENST00000257555.11	TSL:1 MANE Select	c.1502-695A>C		intron	N/A	ENSP00000257555.5	P20823-1
	HNF1A	ENST00000544413.2	TSL:1	c.1502-695A>C		intron	N/A	ENSP00000438804.1	F5H0K0
	HNF1A	ENST00000540108.1	TSL:1	n.*942-695A>C		intron	N/A	ENSP00000445445.1	P20823-8

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

African (AFR) AF: 0.295 AC: 12196 AN: 41404

American (AMR) AF: 0.478 AC: 7299 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1892 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3795 AN: 5154

South Asian (SAS) AF: 0.634 AC: 3052 AN: 4816

European-Finnish (FIN) AF: 0.538 AC: 5680 AN: 10548

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33245 AN: 67938

Other (OTH) AF: 0.490 AC: 1032 AN: 2104

Alfa AF: 0.472 Hom.: 50038

Bravo AF: 0.440

Asia WGS AF: 0.680 AC: 2361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.046
DANN	Benign	0.38
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.96
Mutation Taster		=100/0	polymorphism (auto)

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: rs1169303; hg19: chr12-121436376;