rs762578

Variant names:

• chr14-22481259-G-T
• rs762578
• ENST00000514473.2:n.207C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000514473.2(TRD-AS1):​n.207C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,504 control chromosomes in the GnomAD database, including 1,598 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 0.12 (1596 hom., cov: 27)
  • Exomes 𝑓: 0.27 (2 hom.)
• Consequence: TRD-AS1 ENST00000514473.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 7 publications found

Genes affected

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

TRA (HGNC:12027):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514473.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRD-AS1	NR_148361.1		n.207C>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRD-AS1	ENST00000514473.2	TSL:2	n.207C>A		non_coding_transcript_exon	Exon 2 of 3
	TRD-AS1	ENST00000556777.2	TSL:3	n.544C>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17926 AN: 151364 Hom.: 1595 Cov.: 27

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.273 AC: 6 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.188 AC XY: 3 AN XY: 16

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.188 AC: 3 AN: 16

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.118 AC: 17915 AN: 151482 Hom.: 1596 Cov.: 27 AF XY: 0.123 AC XY: 9121 AN XY: 74040

African (AFR) AF: 0.0491 AC: 2025 AN: 41224

American (AMR) AF: 0.0883 AC: 1341 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3466

East Asian (EAS) AF: 0.485 AC: 2502 AN: 5156

South Asian (SAS) AF: 0.231 AC: 1110 AN: 4796

European-Finnish (FIN) AF: 0.174 AC: 1819 AN: 10474

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.122 AC: 8281 AN: 67884

Other (OTH) AF: 0.107 AC: 226 AN: 2104

Alfa AF: 0.120 Hom.: 2305

Bravo AF: 0.108

Asia WGS AF: 0.318 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.17

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs762578;

hg19: chr14-22950248;

COSMIC: COSV66606808;