rs16860328

Variant names:

• chr3-185917897-A-G
• rs16860328
• NM_004593.3:c.857-172T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

TRA2B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004593.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRA2B	NM_004593.3	MANE Select	c.857-172T>C		intron	N/A	NP_004584.1
	TRA2B	NM_001243879.2		c.557-172T>C		intron	N/A	NP_001230808.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRA2B	ENST00000453386.7	TSL:1 MANE Select	c.857-172T>C		intron	N/A	ENSP00000416959.2
	TRA2B	ENST00000487615.5	TSL:1	n.4089-172T>C		intron	N/A
	TRA2B	ENST00000492417.5	TSL:1	n.3160-172T>C		intron	N/A

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

African (AFR) AF: 0.298 AC: 12368 AN: 41496

American (AMR) AF: 0.260 AC: 3968 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1139 AN: 3468

East Asian (EAS) AF: 0.154 AC: 801 AN: 5186

South Asian (SAS) AF: 0.271 AC: 1306 AN: 4826

European-Finnish (FIN) AF: 0.383 AC: 4048 AN: 10570

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28449 AN: 67962

Other (OTH) AF: 0.336 AC: 709 AN: 2110

Alfa AF: 0.390 Hom.: 19897

Bravo AF: 0.343

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.79
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16860328; hg19: chr3-185635685;