rs547080919

Variant names:

• chr12-121001362-C-T
• rs547080919
• NM_000545.8:c.*170C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-121001362-C-T
• chr12-121001362-C-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_000545.8(HNF1A):​c.*170C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 820,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). The gene HNF1A is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: HNF1A NM_000545.8 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -2.47
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-121001362-C-T is Benign according to our data. Variant chr12-121001362-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 307463.
• BS2: High AC in GnomAd4 at 34 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.*170C>T		3_prime_UTR	Exon 10 of 10	NP_000536.6
	C12orf43	NM_022895.3	MANE Select	c.*2791G>A		3_prime_UTR	Exon 6 of 6	NP_075046.1
	HNF1A	NM_001306179.2		c.*170C>T		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.*170C>T		3_prime_UTR	Exon 10 of 10	ENSP00000257555.5	P20823-1
	C12orf43	ENST00000288757.7	TSL:1 MANE Select	c.*2791G>A		3_prime_UTR	Exon 6 of 6	ENSP00000288757.5	Q96C57
	HNF1A	ENST00000540108.1	TSL:1	n.*1506C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000445445.1	P20823-8

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000157 AC: 105 AN: 668466 Hom.: 0 Cov.: 9 AF XY: 0.000174 AC XY: 60 AN XY: 343870

African (AFR) AF: 0.000229 AC: 4 AN: 17500

American (AMR) AF: 0.000111 AC: 3 AN: 27000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16222

East Asian (EAS) AF: 0.0000313 AC: 1 AN: 31996

South Asian (SAS) AF: 0.000555 AC: 30 AN: 54016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29854

Middle Eastern (MID) AF: 0.000338 AC: 1 AN: 2960

European-Non Finnish (NFE) AF: 0.000134 AC: 61 AN: 455610

Other (OTH) AF: 0.000150 AC: 5 AN: 33308

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74476

African (AFR) AF: 0.000649 AC: 27 AN: 41576

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000230

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity-onset diabetes of the young (1)
-	1	-	Maturity-onset diabetes of the young type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.016
DANN	Benign	0.61
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism

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: rs547080919; hg19: chr12-121439165;