rs1882149

Variant names:

• chr12-121000339-C-T
• rs1882149
• NM_000545.8:c.1768+712C>T

Variant summary

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

The NM_000545.8(HNF1A):​c.1768+712C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 156,926 control chromosomes in the GnomAD database, including 1,273 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 0.11 (1208 hom., cov: 32)
  • Exomes 𝑓: 0.12 (65 hom.)
• Consequence: HNF1A NM_000545.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 12 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.237 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.1768+712C>T		intron	N/A	NP_000536.6
	HNF1A	NM_001306179.2		c.1789+712C>T		intron	N/A	NP_001293108.2	F5H0K0
	HNF1A	NM_001406915.1		c.1576+712C>T		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.1768+712C>T		intron	N/A	ENSP00000257555.5	P20823-1
	HNF1A	ENST00000544413.2	TSL:1	c.1789+712C>T		intron	N/A	ENSP00000438804.1	F5H0K0
	HNF1A	ENST00000540108.1	TSL:1	n.*1208+712C>T		intron	N/A	ENSP00000445445.1	P20823-8

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16682 AN: 152078 Hom.: 1200 Cov.: 32

Gnomad AFR AF: 0.0997

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.121 AC: 572 AN: 4730 Hom.: 65 AF XY: 0.116 AC XY: 283 AN XY: 2442

African (AFR) AF: 0.100 AC: 1 AN: 10

American (AMR) AF: 0.262 AC: 263 AN: 1004

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 5 AN: 26

East Asian (EAS) AF: 0.00 AC: 0 AN: 94

South Asian (SAS) AF: 0.0447 AC: 16 AN: 358

European-Finnish (FIN) AF: 0.0250 AC: 1 AN: 40

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0899 AC: 271 AN: 3016

Other (OTH) AF: 0.0843 AC: 15 AN: 178

GnomAD4 genome AF: 0.110 AC: 16715 AN: 152196 Hom.: 1208 Cov.: 32 AF XY: 0.108 AC XY: 8011 AN XY: 74410

African (AFR) AF: 0.0999 AC: 4148 AN: 41534

American (AMR) AF: 0.243 AC: 3718 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.0618 AC: 297 AN: 4806

European-Finnish (FIN) AF: 0.0433 AC: 460 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7374 AN: 67998

Other (OTH) AF: 0.116 AC: 246 AN: 2112

Alfa AF: 0.115 Hom.: 586

Bravo AF: 0.128

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.38
PhyloP100		0.20
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: rs1882149; hg19: chr12-121438142;