rs16860328

Positions:

• chr3-185917897-A-G
• chr3-185917897-A-T

Variant summary

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

The NM_004593.3(TRA2B):​c.857-172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,090 control chromosomes in the GnomAD database, including 9,771 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 0.35 (9771 hom., cov: 32)
• Consequence: TRA2B NM_004593.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

Genes affected

TRA2B (HGNC:10781): (transformer 2 beta homolog) This gene encodes a nuclear protein which functions as sequence-specific serine/arginine splicing factor which plays a role in mRNA processing, splicing patterns, and gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

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 (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRA2B	NM_004593.3	c.857-172T>C		intron_variant		ENST00000453386.7	NP_004584.1
TRA2B	NM_001243879.2	c.557-172T>C		intron_variant			NP_001230808.1
TRA2B	XM_047448717.1	c.557-172T>C		intron_variant			XP_047304673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRA2B	ENST00000453386.7	c.857-172T>C		intron_variant		1	NM_004593.3	ENSP00000416959	P2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53338 AN: 151970 Hom.: 9757 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.351 AC: 53375 AN: 152090 Hom.: 9771 Cov.: 32 AF XY: 0.344 AC XY: 25603 AN XY: 74346

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.336

Alfa AF: 0.385 Hom.: 3199

Bravo AF: 0.343

Asia WGS AF: 0.231 AC: 803 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	7.3
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs16860328; hg19: chr3-185635685;