Variant rs201167179 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000545.8(HNF1A):c.1623+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000657 in 1,613,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 1 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.201

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046997637).

BP6

Variant 12-120999412-C-T is Benign according to our data. Variant chr12-120999412-C-T is described in ClinVar as [Benign]. Clinvar id is 135504.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1A	NM_000545.8 linkuse as main transcript	c.1623+23C>T		intron_variant		ENST00000257555.11	NP_000536.6	P20823E0YMI7
HNF1A	XM_024449168.2 linkuse as main transcript	c.1646C>T	p.Pro549Leu	missense_variant	8/9		XP_024304936.1
HNF1A	NM_001306179.2 linkuse as main transcript	c.1623+23C>T		intron_variant			NP_001293108.2	P20823E0YMI7
HNF1A	NM_001406915.1 linkuse as main transcript	c.1431+23C>T		intron_variant			NP_001393844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11 linkuse as main transcript	c.1623+23C>T		intron_variant		1	NM_000545.8	ENSP00000257555.5		A0A0A0MQU7

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000394

AC:

AN:

250964

Hom.:

AF XY:

0.000435

AC XY:

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000688

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000698

AC:

1020

AN:

1461478

Hom.:

Cov.:

AF XY:

0.000667

AC XY:

485

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000875

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000263

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000981

EpiControl

AF:

0.00130

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 rs201167179 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

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.32

CADD

Benign

2.2

DANN

Benign

0.50

DEOGEN2

Benign

0.23

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.047

MetaSVM

Uncertain

0.58

PROVEAN

Benign

0.23

REVEL

Benign

0.15

Sift

Benign

0.45

Sift4G

Uncertain

0.020

Vest4

0.13

MVP

0.43

ClinPred

0.012

GERP RS

-3.6

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