rs12466929

Positions:

• chr2-217115710-G-A

Variant summary

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

The ENST00000695932.1(DIRC3-AS1):​n.509+121692G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,886 control chromosomes in the GnomAD database, including 3,794 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 0.20 (3794 hom., cov: 32)
• Consequence: DIRC3-AS1 ENST00000695932.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

DIRC3-AS1 (HGNC:50636): (DIRC3 antisense RNA 1)

IGFBP-AS1 (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 (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP-AS1	XR_001739169.1	n.11845-43298G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIRC3-AS1	ENST00000695932.1	n.509+121692G>A		intron_variant, non_coding_transcript_variant
DIRC3-AS1	ENST00000695934.1	n.173-37701G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29867 AN: 151768 Hom.: 3786 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.197 AC: 29904 AN: 151886 Hom.: 3794 Cov.: 32 AF XY: 0.205 AC XY: 15226 AN XY: 74244

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.182

Alfa AF: 0.124 Hom.: 2180

Bravo AF: 0.205

Asia WGS AF: 0.350 AC: 1216 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	0.55
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12466929; hg19: chr2-217980433;