rs7953249

Positions:

• chr12-120965921-G-A
• chr12-120965921-G-C

Variant summary

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

The ENST00000646404.1(HNF1A-AS1):​n.302-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,036 control chromosomes in the GnomAD database, including 25,923 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 0.58 (25916 hom., cov: 32)
  • Exomes 𝑓: 0.47 (7 hom.)
• Consequence: HNF1A-AS1 ENST00000646404.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.120965921G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1A-AS1	ENST00000619441.1	n.128+14723C>T		intron_variant		3
HNF1A-AS1	ENST00000646404.1	n.302-6C>T		splice_region_variant, intron_variant
HNF1A-AS1	ENST00000647473.1	n.599-2577C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88282 AN: 151852 Hom.: 25882 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.469 AC: 30 AN: 64 Hom.: 7 Cov.: 0 AF XY: 0.405 AC XY: 17 AN XY: 42

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.581 AC: 88371 AN: 151972 Hom.: 25916 Cov.: 32 AF XY: 0.572 AC XY: 42449 AN XY: 74270

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.558

Alfa AF: 0.568 Hom.: 57404

Bravo AF: 0.593

Asia WGS AF: 0.495 AC: 1725 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	0.79
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7953249; hg19: chr12-121403724;