rs10498054

chr2-217126009-T-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+131991T>C 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 0.0309 in 152,254 control chromosomes in the GnomAD database, including 145 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 0.031 (145 hom., cov: 32)
• Consequence: DIRC3-AS1 ENST00000695932.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

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 (AMR) allele frequency at 95% confidence interval = 0.0888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP-AS1	XR_001739169.1	n.11845-32999T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRC3-AS1	ENST00000695932.1	n.509+131991T>C		intron_variant, non_coding_transcript_variant
DIRC3-AS1	ENST00000695934.1	n.173-27402T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4700 AN: 152136 Hom.: 144 Cov.: 32

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0297

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

GnomAD4 genome AF: 0.0309 AC: 4709 AN: 152254 Hom.: 145 Cov.: 32 AF XY: 0.0318 AC XY: 2365 AN XY: 74438

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.0629

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.0146

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0272 Hom.: 9

Bravo AF: 0.0382

Asia WGS AF: 0.0480 AC: 165 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	2.1
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10498054; hg19: chr2-217990732;