12-120978646-G-A

Variant names:

• chr12-120978646-G-A
• rs776978662
• ENST00000560968.6:n.-123G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_000545.8(HNF1A):​c.-123G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 932,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: HNF1A NM_000545.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.26
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 12-120978646-G-A is Benign according to our data. Variant chr12-120978646-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2898303.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 9 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1A	NM_000545.8	c.-123G>A		5_prime_UTR_variant	Exon 1 of 10	ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2	c.-123G>A		5_prime_UTR_variant	Exon 1 of 10		NP_001293108.2
HNF1A	NM_001406915.1	c.-123G>A		5_prime_UTR_variant	Exon 1 of 9		NP_001393844.1
HNF1A	XM_024449168.2	c.-123G>A		5_prime_UTR_variant	Exon 1 of 9		XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11	c.-123G>A		5_prime_UTR_variant	Exon 1 of 10	1	NM_000545.8	ENSP00000257555.5

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152120 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000193

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000419 AC: 8 AN: 191046 AF XY: 0.0000373

Gnomad AFR exome AF: 0.000458

Gnomad AMR exome AF: 0.0000326

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000240

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000218 AC: 17 AN: 780536 Hom.: 0 Cov.: 10 AF XY: 0.0000194 AC XY: 8 AN XY: 412988

African (AFR) AF: 0.000192 AC: 4 AN: 20786

American (AMR) AF: 0.0000245 AC: 1 AN: 40852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21650

East Asian (EAS) AF: 0.00 AC: 0 AN: 35486

South Asian (SAS) AF: 0.00 AC: 0 AN: 70110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37768

Middle Eastern (MID) AF: 0.000260 AC: 1 AN: 3846

European-Non Finnish (NFE) AF: 0.0000176 AC: 9 AN: 511848

Other (OTH) AF: 0.0000524 AC: 2 AN: 38190

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152120 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74316

African (AFR) AF: 0.000193 AC: 8 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.97
PhyloP100		3.3
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.1

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

Other links and lift over

dbSNP: rs776978662; hg19: chr12-121416449;