rs1169310

Variant names:

• chr12-121001630-G-A
• rs1169310
• NM_000545.8:c.*438G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-121001630-G-A
• chr12-121001630-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.*438G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 441,510 control chromosomes in the GnomAD database, including 32,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene HNF1A is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.32 (8635 hom., cov: 31)
  • Exomes 𝑓: 0.40 (24288 hom.)
• Consequence: HNF1A NM_000545.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.148
• Publications: 59 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]

C12orf43 (HGNC:25719): (chromosome 12 open reading frame 43) Predicted to be involved in Spemann organizer formation and negative regulation of Wnt signaling pathway. Predicted to be located in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Specifications for HNF1A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-121001630-G-A is Benign according to our data. Variant chr12-121001630-G-A is described in ClinVar as Benign. ClinVar VariationId is 307468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 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.*438G>A		3_prime_UTR	Exon 10 of 10	NP_000536.6
	C12orf43	NM_022895.3	MANE Select	c.*2523C>T		3_prime_UTR	Exon 6 of 6	NP_075046.1
	HNF1A	NM_001306179.2		c.*438G>A		3_prime_UTR	Exon 10 of 10	NP_001293108.2	F5H0K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1A	ENST00000257555.11	TSL:1 MANE Select	c.*438G>A		3_prime_UTR	Exon 10 of 10	ENSP00000257555.5	P20823-1
	C12orf43	ENST00000288757.7	TSL:1 MANE Select	c.*2523C>T		3_prime_UTR	Exon 6 of 6	ENSP00000288757.5	Q96C57
	HNF1A	ENST00000540108.1	TSL:1	n.*1774G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000445445.1	P20823-8

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48258 AN: 151810 Hom.: 8632 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.398 AC: 115123 AN: 289584 Hom.: 24288 Cov.: 0 AF XY: 0.411 AC XY: 62495 AN XY: 151962

African (AFR) AF: 0.145 AC: 1360 AN: 9376

American (AMR) AF: 0.397 AC: 5783 AN: 14556

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 4980 AN: 9768

East Asian (EAS) AF: 0.525 AC: 10320 AN: 19662

South Asian (SAS) AF: 0.517 AC: 23042 AN: 44580

European-Finnish (FIN) AF: 0.360 AC: 3241 AN: 9012

Middle Eastern (MID) AF: 0.568 AC: 1599 AN: 2814

European-Non Finnish (NFE) AF: 0.359 AC: 58434 AN: 162976

Other (OTH) AF: 0.378 AC: 6364 AN: 16840

GnomAD4 genome AF: 0.318 AC: 48259 AN: 151926 Hom.: 8635 Cov.: 31 AF XY: 0.327 AC XY: 24249 AN XY: 74228

African (AFR) AF: 0.146 AC: 6038 AN: 41478

American (AMR) AF: 0.392 AC: 5989 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1751 AN: 3456

East Asian (EAS) AF: 0.490 AC: 2511 AN: 5128

South Asian (SAS) AF: 0.512 AC: 2472 AN: 4824

European-Finnish (FIN) AF: 0.384 AC: 4056 AN: 10554

Middle Eastern (MID) AF: 0.569 AC: 165 AN: 290

European-Non Finnish (NFE) AF: 0.356 AC: 24146 AN: 67906

Other (OTH) AF: 0.373 AC: 786 AN: 2110

Alfa AF: 0.342 Hom.: 24298

Bravo AF: 0.309

Asia WGS AF: 0.479 AC: 1663 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity-onset diabetes of the young type 3 (1)
-	-	1	not provided (1)
-	-	1	Type 2 diabetes mellitus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.98
DANN	Benign	0.51
PhyloP100		-0.15
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: rs1169310; hg19: chr12-121439433; COSMIC: COSV99982345; COSMIC: COSV99982345;