Genetic Variant NM_000545.8:c.-119delG (chr12-120978643-TG-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000545.8(HNF1A):c.-119delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 895,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

HNF1A
NM_000545.8 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 1.38

Publications

1 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:

HNF1A-AS1 (HGNC:26785): (HNF1A antisense RNA 1)

HNF1A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 5 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000545.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF1A	NM_000545.8	MANE Select	c.-119delG	5_prime_UTR	Exon 1 of 10	NP_000536.6
HNF1A	NM_001306179.2		c.-119delG	5_prime_UTR	Exon 1 of 10	NP_001293108.2	F5H0K0
HNF1A	NM_001406915.1		c.-119delG	5_prime_UTR	Exon 1 of 9	NP_001393844.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF1A	ENST00000257555.11	TSL:1 MANE Select	c.-119delG	5_prime_UTR	Exon 1 of 10	ENSP00000257555.5	P20823-1
HNF1A	ENST00000560968.6	TSL:1	n.-119delG	non_coding_transcript_exon	Exon 1 of 10	ENSP00000453965.2	E0YMI8
HNF1A	ENST00000560968.6	TSL:1	n.-119delG	5_prime_UTR	Exon 1 of 10	ENSP00000453965.2	E0YMI8

Frequencies

GnomAD3 genomes

AF:

0.00000733

AC:

AN:

136356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000160

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

184158

AF XY:

0.0000194

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000376

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000659

AC:

AN:

759062

Hom.:

Cov.:

AF XY:

0.00000745

AC XY:

AN XY:

402436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20330

American (AMR)

AF:

0.00

AC:

AN:

40166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21392

East Asian (EAS)

AF:

0.0000285

AC:

AN:

35126

South Asian (SAS)

AF:

0.00

AC:

AN:

69414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3650

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

494300

Other (OTH)

AF:

0.00

AC:

AN:

37444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000733

AC:

AN:

136356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35802

American (AMR)

AF:

0.00

AC:

AN:

13790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3222

East Asian (EAS)

AF:

0.00

AC:

AN:

4600

South Asian (SAS)

AF:

0.00

AC:

AN:

4254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000160

AC:

AN:

62646

Other (OTH)

AF:

0.00

AC:

AN:

1856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Maturity-onset diabetes of the young type 3 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=29/271

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over