14-22446824-G-T

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+34417C>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 0.133 in 150,182 control chromosomes in the GnomAD database, including 1,796 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 0.13 (1796 hom., cov: 25)
• Consequence: TRD-AS1 NR_148361.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRD-AS1	NR_148361.1	n.225+34417C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRD-AS1	ENST00000514473.2	n.225+34417C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20053 AN: 150064 Hom.: 1801 Cov.: 25

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.133 AC: 20040 AN: 150182 Hom.: 1796 Cov.: 25 AF XY: 0.139 AC XY: 10219 AN XY: 73320

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.118

Alfa AF: 0.127 Hom.: 1733

Bravo AF: 0.126

Asia WGS AF: 0.334 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.5
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12147516; hg19: chr14-22915816;