dbSNP rs1882149: HNF1A:c.1768+712C>T (chr12-121000339-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000545.8(HNF1A):c.1768+712C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 156,926 control chromosomes in the GnomAD database, including 1,273 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1208 hom., cov: 32)

Exomes 𝑓: 0.12 ( 65 hom. )

Consequence

HNF1A
NM_000545.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.197

Publications

12 publications found

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:

C12orf43 (HGNC:25719): (chromosome 12 open reading frame 43) Predicted to be involved in Spemann organizer formation and negative regulation of Wnt signaling pathway. Predicted to be located in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

C12orf43 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1A	NM_000545.8 link	c.1768+712C>T		intron_variant	Intron 9 of 9	ENST00000257555.11	NP_000536.6	P20823E0YMI7
C12orf43	NM_022895.3 link	c.*3814G>A		downstream_gene_variant		ENST00000288757.7	NP_075046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11 link	c.1768+712C>T		intron_variant	Intron 9 of 9	1	NM_000545.8	ENSP00000257555.5		A0A0A0MQU7
C12orf43	ENST00000288757.7 link	c.*3814G>A		downstream_gene_variant		1	NM_022895.3	ENSP00000288757.5		Q96C57

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16682

AN:

152078

Hom.:

1200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0997

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.0965

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0613

Gnomad FIN

AF:

0.0433

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.121

AC:

572

AN:

4730

Hom.:

AF XY:

0.116

AC XY:

283

AN XY:

2442

show subpopulations

African (AFR)

AF:

0.100

AC:

AN:

American (AMR)

AF:

0.262

AC:

263

AN:

1004

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0447

AC:

AN:

358

European-Finnish (FIN)

AF:

0.0250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0899

AC:

271

AN:

3016

Other (OTH)

AF:

0.0843

AC:

AN:

178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.110

AC:

16715

AN:

152196

Hom.:

1208

Cov.:

AF XY:

0.108

AC XY:

8011

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0999

AC:

4148

AN:

41534

American (AMR)

AF:

0.243

AC:

3718

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0965

AC:

335

AN:

3470

East Asian (EAS)

AF:

0.00155

AC:

AN:

5174

South Asian (SAS)

AF:

0.0618

AC:

297

AN:

4806

European-Finnish (FIN)

AF:

0.0433

AC:

460

AN:

10616

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7374

AN:

67998

Other (OTH)

AF:

0.116

AC:

246

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

723

1445

2168

2890

3613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.115

Hom.:

586

Bravo

AF:

0.128

Asia WGS

AF:

0.0440

AC:

155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.8

(source)

DANN

Benign

0.38

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over