12-120996827-CTCAT-CTCATTCATTCATTCATTCAT

Variant names:

• chr12-120996827-C-CTCATTCATTCATTCAT
• rs58371019
• NM_000545.8:c.1309+86_1309+101dupTCATTCATTCATTCAT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000545.8(HNF1A):​c.1309+86_1309+101dupTCATTCATTCATTCAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000196 in 1,530,582 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000021 (1 hom.)
• Consequence: HNF1A NM_000545.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.434
• Publications: 8 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 12-120996827-C-CTCATTCATTCATTCAT is Benign according to our data. Variant chr12-120996827-C-CTCATTCATTCATTCAT is described in ClinVar as Benign. ClinVar VariationId is 1801507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 29 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.1309+86_1309+101dupTCATTCATTCATTCAT		intron	N/A	NP_000536.6
	HNF1A	NM_001306179.2		c.1309+86_1309+101dupTCATTCATTCATTCAT		intron	N/A	NP_001293108.2	F5H0K0
	HNF1A	NM_001406915.1		c.1309+86_1309+101dupTCATTCATTCATTCAT		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.1309+86_1309+101dupTCATTCATTCATTCAT		intron	N/A	ENSP00000257555.5	P20823-1
	HNF1A	ENST00000544413.2	TSL:1	c.1309+86_1309+101dupTCATTCATTCATTCAT		intron	N/A	ENSP00000438804.1	F5H0K0
	HNF1A	ENST00000535955.5	TSL:1	n.43-663_43-648dupTCATTCATTCATTCAT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150778 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000654 AC: 10 AN: 152926 AF XY: 0.0000733

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000210 AC: 29 AN: 1379804 Hom.: 1 Cov.: 39 AF XY: 0.0000264 AC XY: 18 AN XY: 681818

African (AFR) AF: 0.00 AC: 0 AN: 31714

American (AMR) AF: 0.00 AC: 0 AN: 35754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24860

East Asian (EAS) AF: 0.00 AC: 0 AN: 35508

South Asian (SAS) AF: 0.000253 AC: 20 AN: 78910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48654

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5600

European-Non Finnish (NFE) AF: 0.00000377 AC: 4 AN: 1061466

Other (OTH) AF: 0.0000698 AC: 4 AN: 57338

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150778 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 1 AN XY: 73566

African (AFR) AF: 0.00 AC: 0 AN: 40988

American (AMR) AF: 0.00 AC: 0 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67594

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 4223

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity-onset diabetes of the young (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43
Mutation Taster		=188/12	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58371019; hg19: chr12-121434630;