rs6721996

Positions:

• chr2-217044740-G-A
• chr2-217044740-G-C

Variant summary

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

The ENST00000695932.1(DIRC3-AS1):​n.509+50722G>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 0.492 in 151,964 control chromosomes in the GnomAD database, including 19,190 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 0.49 (19190 hom., cov: 33)
• Consequence: DIRC3-AS1 ENST00000695932.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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 = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP-AS1	XR_001739169.1	n.11844+50722G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRC3-AS1	ENST00000695932.1	n.509+50722G>A		intron_variant, non_coding_transcript_variant
DIRC3-AS1	ENST00000695934.1	n.172+50722G>A		intron_variant, non_coding_transcript_variant
DIRC3-AS1	ENST00000695937.1	n.289+7460G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74648 AN: 151844 Hom.: 19166 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.492 AC: 74714 AN: 151964 Hom.: 19190 Cov.: 33 AF XY: 0.493 AC XY: 36633 AN XY: 74254

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.901

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.508

Alfa AF: 0.504 Hom.: 6956

Bravo AF: 0.500

Asia WGS AF: 0.726 AC: 2521 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	0.38
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6721996; hg19: chr2-217909463;