rs6588505

Variant names:

• chr1-47789110-C-T
• rs6588505
• NM_001194986.2:c.988+5476G>A

Variant summary

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

The NM_001194986.2(TRABD2B):​c.988+5476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,086 control chromosomes in the GnomAD database, including 7,185 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 0.30 (7185 hom., cov: 32)
• Consequence: TRABD2B NM_001194986.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 3 publications found

Genes affected

TRABD2B (HGNC:44200): (TraB domain containing 2B) Enables Wnt-protein binding activity and metalloendopeptidase activity. Involved in several processes, including negative regulation of Wnt signaling pathway; positive regulation of protein oxidation; and positive regulation of protein-containing complex assembly. Is integral component of organelle membrane and integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRABD2B	NM_001194986.2	c.988+5476G>A		intron_variant	Intron 4 of 6	ENST00000606738.3	NP_001181915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRABD2B	ENST00000606738.3	c.988+5476G>A		intron_variant	Intron 4 of 6	1	NM_001194986.2	ENSP00000476820.1
TRABD2B	ENST00000435576.2	n.327-10566G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45057 AN: 151968 Hom.: 7148 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.297 AC: 45155 AN: 152086 Hom.: 7185 Cov.: 32 AF XY: 0.298 AC XY: 22179 AN XY: 74346

African (AFR) AF: 0.389 AC: 16151 AN: 41476

American (AMR) AF: 0.303 AC: 4625 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3468

East Asian (EAS) AF: 0.466 AC: 2404 AN: 5160

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4812

European-Finnish (FIN) AF: 0.296 AC: 3134 AN: 10582

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15812 AN: 67998

Other (OTH) AF: 0.297 AC: 629 AN: 2116

Alfa AF: 0.253 Hom.: 21248

Bravo AF: 0.301

Asia WGS AF: 0.368 AC: 1278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.48
PhyloP100		-1.4
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: rs6588505; hg19: chr1-48254782; COSMIC: COSV71108357;