rs1169286

Variant names:

• chr12-120981253-T-C
• rs1169286
• NM_000545.8:c.326+2159T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-120981253-T-C
• chr12-120981253-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000545.8(HNF1A):​c.326+2159T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,064 control chromosomes in the GnomAD database, including 13,198 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 0.40 (13198 hom., cov: 32)
• Consequence: HNF1A NM_000545.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 22 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1A	NM_000545.8	c.326+2159T>C		intron_variant	Intron 1 of 9	ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2	c.326+2159T>C		intron_variant	Intron 1 of 9		NP_001293108.2
HNF1A	NM_001406915.1	c.326+2159T>C		intron_variant	Intron 1 of 8		NP_001393844.1
HNF1A	XM_024449168.2	c.326+2159T>C		intron_variant	Intron 1 of 8		XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11	c.326+2159T>C		intron_variant	Intron 1 of 9	1	NM_000545.8	ENSP00000257555.5

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60859 AN: 151944 Hom.: 13182 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.400 AC: 60896 AN: 152064 Hom.: 13198 Cov.: 32 AF XY: 0.407 AC XY: 30268 AN XY: 74318

African (AFR) AF: 0.240 AC: 9951 AN: 41506

American (AMR) AF: 0.586 AC: 8951 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2432 AN: 5146

South Asian (SAS) AF: 0.465 AC: 2242 AN: 4822

European-Finnish (FIN) AF: 0.431 AC: 4557 AN: 10580

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29287 AN: 67940

Other (OTH) AF: 0.437 AC: 923 AN: 2112

Alfa AF: 0.422 Hom.: 35882

Bravo AF: 0.406

Asia WGS AF: 0.468 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.76
PhyloP100		0.46
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: rs1169286; hg19: chr12-121419056;