rs1169293

chr12-120988742-G-Achr12-120988742-G-Cchr12-120988742-G-T

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.327-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 1,153,512 control chromosomes in the GnomAD database, including 489,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (61428 hom., cov: 33)
  • Exomes 𝑓: 0.92 (427939 hom.)
• Consequence: HNF1A NM_000545.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.297

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=-0.82).
• BP6: Variant 12-120988742-G-A is Benign according to our data. Variant chr12-120988742-G-A is described in ClinVar as [Benign]. Clinvar id is 1232183.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-120988742-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1A	NM_000545.8	c.327-91G>A		intron_variant		ENST00000257555.11
HNF1A	NM_001306179.2	c.327-91G>A		intron_variant
HNF1A	NM_001406915.1	c.327-91G>A		intron_variant
HNF1A	XM_024449168.2	c.327-91G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11	c.327-91G>A		intron_variant		1	NM_000545.8	P4

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136383 AN: 152084 Hom.: 61375 Cov.: 33

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.894

GnomAD4 exome AF: 0.924 AC: 925122 AN: 1001310 Hom.: 427939 AF XY: 0.922 AC XY: 472522 AN XY: 512504

Gnomad4 AFR exome AF: 0.805

Gnomad4 AMR exome AF: 0.947

Gnomad4 ASJ exome AF: 0.946

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.935

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.923

GnomAD4 genome AF: 0.897 AC: 136496 AN: 152202 Hom.: 61428 Cov.: 33 AF XY: 0.898 AC XY: 66800 AN XY: 74414

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.895

Alfa AF: 0.922 Hom.: 103339

Bravo AF: 0.892

Asia WGS AF: 0.922 AC: 3207 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 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.6
Dann	Benign	0.69

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: rs1169293; hg19: chr12-121426545;