rs1169300

chr12-120993422-G-Achr12-120993422-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 0.0730

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 -14 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 id is 676874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1A	NM_000545.8	c.527-98G>A		intron_variant		ENST00000257555.11
HNF1A	NM_001306179.2	c.527-98G>A		intron_variant
HNF1A	NM_001406915.1	c.527-98G>A		intron_variant
HNF1A	XM_024449168.2	c.527-98G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11	c.527-98G>A		intron_variant		1	NM_000545.8	P4

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

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.374

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.340

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

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.314

Alfa AF: 0.308 Hom.: 15809

Bravo AF: 0.269

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.9
Dann	Benign	0.48

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: rs1169300; hg19: chr12-121431225; COSMIC: COSV57462420; COSMIC: COSV57462420;