Variant 12-120996794-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000545.8(HNF1A):c.1309+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,602,842 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 10 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -2.57

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=-0.89).

BP6

Variant 12-120996794-C-T is Benign according to our data. Variant chr12-120996794-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 133354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00539 (818/151674) while in subpopulation AFR AF= 0.0186 (771/41410). AF 95% confidence interval is 0.0175. There are 5 homozygotes in gnomad4. There are 360 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 818 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HNF1A	NM_000545.8 linkuse as main transcript	c.1309+52C>T	intron_variant	ENST00000257555.11
HNF1A	NM_001306179.2 linkuse as main transcript	c.1309+52C>T	intron_variant
HNF1A	NM_001406915.1 linkuse as main transcript	c.1309+52C>T	intron_variant
HNF1A	XM_024449168.2 linkuse as main transcript	c.1309+52C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11 linkuse as main transcript	c.1309+52C>T		intron_variant		1	NM_000545.8	P4

Frequencies

GnomAD3 genomes

AF:

0.00540

AC:

818

AN:

151556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00152

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000280

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.00148

AC:

334

AN:

225742

Hom.:

AF XY:

0.00112

AC XY:

137

AN XY:

122358

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.000906

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000181

Gnomad OTH exome

AF:

0.000713

GnomAD4 exome

AF:

0.000686

AC:

995

AN:

1451168

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

435

AN XY:

721050

show subpopulations

Gnomad4 AFR exome

AF:

0.0193

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000355

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000213

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00539

AC:

818

AN:

151674

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

360

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000280

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00204

Hom.:

Bravo

AF:

0.00615

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Maturity onset diabetes mellitus in young

Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs56031130 with MODY3. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 16, 2018

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.041

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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