Variant rs2071190 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000545.8(HNF1A):c.527-51T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,571,250 control chromosomes in the GnomAD database, including 47,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4847 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42560 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.613

Variant links:

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]

HNF1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-120993469-T-A is Benign according to our data. Variant chr12-120993469-T-A is described in ClinVar as [Benign]. Clinvar id is 674357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-120993469-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HNF1A	NM_000545.8 linkuse as main transcript	c.527-51T>A	intron_variant	ENST00000257555.11
HNF1A	NM_001306179.2 linkuse as main transcript	c.527-51T>A	intron_variant
HNF1A	NM_001406915.1 linkuse as main transcript	c.527-51T>A	intron_variant
HNF1A	XM_024449168.2 linkuse as main transcript	c.527-51T>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11 linkuse as main transcript	c.527-51T>A		intron_variant		1	NM_000545.8	P4

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37253

AN:

151920

Hom.:

4829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.241

GnomAD3 exomes

AF:

0.244

AC:

59588

AN:

243864

Hom.:

7921

AF XY:

0.234

AC XY:

30754

AN XY:

131686

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.164

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.240

AC:

341185

AN:

1419214

Hom.:

42560

Cov.:

AF XY:

0.236

AC XY:

167246

AN XY:

707948

show subpopulations

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.392

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.245

AC:

37314

AN:

152036

Hom.:

4847

Cov.:

AF XY:

0.243

AC XY:

18066

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.197

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.219

Hom.:

700

Bravo

AF:

0.258

Asia WGS

AF:

0.244

AC:

848

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 17, 2023	- -
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

-0.84

CADD

Benign

0.040

DANN

Benign

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over