rs1169300

Variant names:

• chr12-120993422-G-A
• rs1169300
• NM_000545.8:c.527-98G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-120993422-G-A
• chr12-120993422-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000545.8(HNF1A):​c.527-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,215,012 control chromosomes in the GnomAD database, including 66,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6438 hom., cov: 32)
  • Exomes 𝑓: 0.33 (60252 hom.)
• Consequence: HNF1A NM_000545.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0730
• Publications: 45 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-120993422-G-A is Benign according to our data. Variant chr12-120993422-G-A is described in ClinVar as Benign. ClinVar VariationId is 676874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 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.527-98G>A		intron	N/A	NP_000536.6
	HNF1A	NM_001306179.2		c.527-98G>A		intron	N/A	NP_001293108.2	F5H0K0
	HNF1A	NM_001406915.1		c.527-98G>A		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.527-98G>A		intron	N/A	ENSP00000257555.5	P20823-1
	HNF1A	ENST00000544413.2	TSL:1	c.527-98G>A		intron	N/A	ENSP00000438804.1	F5H0K0
	HNF1A	ENST00000535955.5	TSL:1	n.43-4069G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41605 AN: 151968 Hom.: 6435 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.332 AC: 352809 AN: 1062926 Hom.: 60252 AF XY: 0.335 AC XY: 181170 AN XY: 541266

African (AFR) AF: 0.131 AC: 3318 AN: 25292

American (AMR) AF: 0.374 AC: 13863 AN: 37068

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 11082 AN: 23388

East Asian (EAS) AF: 0.528 AC: 19252 AN: 36496

South Asian (SAS) AF: 0.416 AC: 31048 AN: 74560

European-Finnish (FIN) AF: 0.309 AC: 14283 AN: 46284

Middle Eastern (MID) AF: 0.469 AC: 1662 AN: 3544

European-Non Finnish (NFE) AF: 0.315 AC: 242206 AN: 768992

Other (OTH) AF: 0.340 AC: 16095 AN: 47302

GnomAD4 genome AF: 0.274 AC: 41609 AN: 152086 Hom.: 6438 Cov.: 32 AF XY: 0.281 AC XY: 20893 AN XY: 74330

African (AFR) AF: 0.131 AC: 5441 AN: 41510

American (AMR) AF: 0.344 AC: 5264 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1594 AN: 3472

East Asian (EAS) AF: 0.486 AC: 2510 AN: 5164

South Asian (SAS) AF: 0.403 AC: 1943 AN: 4824

European-Finnish (FIN) AF: 0.321 AC: 3390 AN: 10556

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20334 AN: 67962

Other (OTH) AF: 0.314 AC: 662 AN: 2110

Alfa AF: 0.297 Hom.: 23357

Bravo AF: 0.269

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		0.073
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: rs1169300; hg19: chr12-121431225; COSMIC: COSV57462420; COSMIC: COSV57462420;