rs2733776

Positions:

• chr14-22461795-A-G

Variant summary

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

The NR_148361.1(TRD-AS1):​n.225+19446T>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 0.243 in 151,054 control chromosomes in the GnomAD database, including 4,671 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 0.24 (4671 hom., cov: 26)
• Consequence: TRD-AS1 NR_148361.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

Genes affected

TRD-AS1 (HGNC:56197): (TRD antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRD-AS1	NR_148361.1	n.225+19446T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRD-AS1	ENST00000514473.2	n.225+19446T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36621 AN: 150936 Hom.: 4668 Cov.: 26

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.243 AC: 36656 AN: 151054 Hom.: 4671 Cov.: 26 AF XY: 0.243 AC XY: 17949 AN XY: 73806

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.240

Alfa AF: 0.281 Hom.: 3110

Bravo AF: 0.233

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2733776; hg19: chr14-22930787;