rs1882149

chr12-121000339-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1A	NM_000545.8	c.1768+712C>T		intron_variant		ENST00000257555.11
HNF1A	NM_001306179.2	c.1789+712C>T		intron_variant
HNF1A	NM_001406915.1	c.1576+712C>T		intron_variant
HNF1A	XM_024449168.2	c.1861+712C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11	c.1768+712C>T		intron_variant		1	NM_000545.8	P4

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

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0447

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.0899

Gnomad4 OTH exome AF: 0.0843

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

Gnomad4 AFR AF: 0.0999

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0618

Gnomad4 FIN AF: 0.0433

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.116

Alfa AF: 0.106 Hom.: 208

Bravo AF: 0.128

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.8
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs1882149; hg19: chr12-121438142;