2-216760956-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000695932.1(DIRC3-AS1):n.448+48487G>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 0.0105 in 152,068 control chromosomes in the GnomAD database, including 23 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 0.011 (23 hom., cov: 32)
• Consequence: DIRC3-AS1 ENST00000695932.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426

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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1604/152068) while in subpopulation AFR AF= 0.0349 (1446/41466). AF 95% confidence interval is 0.0334. There are 23 homozygotes in gnomad4. There are 742 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP-AS1	XR_001739169.1	n.482-3933G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIRC3-AS1	ENST00000695932.1	n.448+48487G>C		intron_variant, non_coding_transcript_variant
DIRC3-AS1	ENST00000447289.1	n.389-3933G>C		intron_variant, non_coding_transcript_variant		5
DIRC3-AS1	ENST00000695934.1	n.111+48487G>C		intron_variant, non_coding_transcript_variant
DIRC3-AS1	ENST00000702642.1	n.324-38593G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1601 AN: 151950 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00908

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

GnomAD4 genome AF: 0.0105 AC: 1604 AN: 152068 Hom.: 23 Cov.: 32 AF XY: 0.00998 AC XY: 742 AN XY: 74316

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00899

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.9
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13020935; hg19: chr2-217625679;