14-22434470-A-G

Variant names:

• chr14-22434470-A-G
• rs2141988

Variant summary

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

The variant allele was found at a frequency of 0.444 in 150,360 control chromosomes in the GnomAD database, including 15,545 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 0.44 (15545 hom., cov: 25)
• Consequence: TRA intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792
• Publications: 6 publications found

Genes affected

TRA (HGNC:12027):

TRD (HGNC:12252):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRA		n.22434470A>G		intragenic_variant
TRD		n.22434470A>G		intragenic_variant
TRD-AS1	NR_148361.1	n.225+46771T>C		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRD-AS1	ENST00000514473.2	n.225+46771T>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 66697 AN: 150242 Hom.: 15547 Cov.: 25

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.444 AC: 66720 AN: 150360 Hom.: 15545 Cov.: 25 AF XY: 0.448 AC XY: 32915 AN XY: 73434

African (AFR) AF: 0.320 AC: 13060 AN: 40766

American (AMR) AF: 0.365 AC: 5466 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1923 AN: 3456

East Asian (EAS) AF: 0.692 AC: 3569 AN: 5156

South Asian (SAS) AF: 0.642 AC: 3040 AN: 4734

European-Finnish (FIN) AF: 0.495 AC: 5107 AN: 10322

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 32982 AN: 67666

Other (OTH) AF: 0.420 AC: 879 AN: 2092

Alfa AF: 0.471 Hom.: 30014

Bravo AF: 0.423

Asia WGS AF: 0.647 AC: 2248 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.51
PhyloP100		0.79

Splicing

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

Other links and lift over

dbSNP: rs2141988; hg19: chr14-22903462;