rs12080929

Variant names:

• chr1-47970476-T-C
• rs12080929
• NM_001194986.2:c.666+23558A>G

Variant summary

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

The NM_001194986.2(TRABD2B):​c.666+23558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,018 control chromosomes in the GnomAD database, including 4,641 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 0.24 (4641 hom., cov: 32)
• Consequence: TRABD2B NM_001194986.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRABD2B	NM_001194986.2	c.666+23558A>G		intron_variant	Intron 2 of 6	ENST00000606738.3	NP_001181915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRABD2B	ENST00000606738.3	c.666+23558A>G		intron_variant	Intron 2 of 6	1	NM_001194986.2	ENSP00000476820.1
TRABD2B	ENST00000435576.2	n.179+23558A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36937 AN: 151900 Hom.: 4639 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.243 AC: 36958 AN: 152018 Hom.: 4641 Cov.: 32 AF XY: 0.243 AC XY: 18049 AN XY: 74298

African (AFR) AF: 0.196 AC: 8122 AN: 41484

American (AMR) AF: 0.228 AC: 3480 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3468

East Asian (EAS) AF: 0.271 AC: 1396 AN: 5158

South Asian (SAS) AF: 0.164 AC: 790 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3345 AN: 10568

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17964 AN: 67934

Other (OTH) AF: 0.250 AC: 527 AN: 2108

Alfa AF: 0.245 Hom.: 725

Bravo AF: 0.237

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.75
PhyloP100		0.55
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: rs12080929; hg19: chr1-48436148;