Variant rs587777933 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_000545.8(HNF1A):c.1309+184dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,506,614 control chromosomes in the GnomAD database, including 58 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 18 hom., cov: 31)

Exomes 𝑓: 0.0044 ( 40 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.992

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 12-120996922-C-CA is Benign according to our data. Variant chr12-120996922-C-CA is described in ClinVar as [Benign]. Clinvar id is 135500.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 797 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HNF1A	NM_000545.8 linkuse as main transcript	c.1309+184dup	intron_variant	ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2 linkuse as main transcript	c.1309+184dup	intron_variant		NP_001293108.2
HNF1A	NM_001406915.1 linkuse as main transcript	c.1309+184dup	intron_variant		NP_001393844.1
HNF1A	XM_024449168.2 linkuse as main transcript	c.1309+184dup	intron_variant		XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11 linkuse as main transcript	c.1309+184dup		intron_variant		1	NM_000545.8	ENSP00000257555	P4

Frequencies

GnomAD3 genomes

AF:

0.00525

AC:

797

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000581

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00494

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00573

AC:

843

AN:

147196

Hom.:

AF XY:

0.00523

AC XY:

415

AN XY:

79328

show subpopulations

Gnomad AFR exome

AF:

0.000441

Gnomad AMR exome

AF:

0.00216

Gnomad ASJ exome

AF:

0.00525

Gnomad EAS exome

AF:

0.0000917

Gnomad SAS exome

AF:

0.0000444

Gnomad FIN exome

AF:

0.0334

Gnomad NFE exome

AF:

0.00393

Gnomad OTH exome

AF:

0.00351

GnomAD4 exome

AF:

0.00441

AC:

5968

AN:

1354650

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

2910

AN XY:

670342

show subpopulations

Gnomad4 AFR exome

AF:

0.000615

Gnomad4 AMR exome

AF:

0.00200

Gnomad4 ASJ exome

AF:

0.00539

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000645

Gnomad4 FIN exome

AF:

0.0309

Gnomad4 NFE exome

AF:

0.00394

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

AF:

0.00524

AC:

797

AN:

151964

Hom.:

Cov.:

AF XY:

0.00626

AC XY:

465

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.000579

Gnomad4 AMR

AF:

0.00282

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0345

Gnomad4 NFE

AF:

0.00494

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00437

Hom.:

Bravo

AF:

0.00265

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

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 rs201039488 with MODY3. -

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

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