rs2393775

Positions:

• chr12-120986771-G-A
• chr12-120986771-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000257555.11(HNF1A):​c.327-2062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,908 control chromosomes in the GnomAD database, including 28,843 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 0.61 (28843 hom., cov: 31)
• Consequence: HNF1A ENST00000257555.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1A	NM_000545.8	c.327-2062G>A		intron_variant		ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2	c.327-2062G>A		intron_variant			NP_001293108.2
HNF1A	NM_001406915.1	c.327-2062G>A		intron_variant			NP_001393844.1
HNF1A	XM_024449168.2	c.327-2062G>A		intron_variant			XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11	c.327-2062G>A		intron_variant		1	NM_000545.8	ENSP00000257555	P4

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93199 AN: 151790 Hom.: 28798 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.594

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.614 AC: 93301 AN: 151908 Hom.: 28843 Cov.: 31 AF XY: 0.606 AC XY: 44965 AN XY: 74238

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.589

Alfa AF: 0.614 Hom.: 3423

Bravo AF: 0.621

Asia WGS AF: 0.530 AC: 1846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs2393775; hg19: chr12-121424574;