1-218345173-A-C

Position:

• chr1-218345173-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_Moderate BP6_Very_Strong BA1

The NR_046268.1(TGFB2-AS1):​n.290+2T>G variant causes a splice donor, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,360 control chromosomes in the GnomAD database, including 6,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (6580 hom., cov: 32)
  • Exomes 𝑓: 0.083 (4 hom.)
• Consequence: TGFB2-AS1 NR_046268.1 splice_donor, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.326

Genes affected

TGFB2-AS1 (HGNC:50628): (TGFB2 antisense RNA 1 (head to head))

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene.
• BP6: Variant 1-218345173-A-C is Benign according to our data. Variant chr1-218345173-A-C is described in ClinVar as [Benign]. Clinvar id is 1241729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGFB2-AS1	NR_046268.1	n.290+2T>G		splice_donor_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGFB2-AS1	ENST00000689961.2	n.650T>G		non_coding_transcript_exon_variant	2/3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28029 AN: 152086 Hom.: 6555 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.0827

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.0833 AC: 13 AN: 156 Hom.: 4 Cov.: 0 AF XY: 0.0789 AC XY: 9 AN XY: 114

Gnomad4 AFR exome AF: 0.750

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0268

Gnomad4 OTH exome AF: 0.0500

GnomAD4 genome AF: 0.185 AC: 28106 AN: 152204 Hom.: 6580 Cov.: 32 AF XY: 0.178 AC XY: 13219 AN XY: 74418

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.0887

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.0827

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0222

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.135

Alfa AF: 0.107 Hom.: 1259

Bravo AF: 0.208

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	13
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7550232; hg19: chr1-218518515;