1-47774333-T-C

Variant names:

• chr1-47774333-T-C
• rs2282361
• NM_001194986.2:c.1349+837A>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.1349+837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,048 control chromosomes in the GnomAD database, including 15,172 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 (15172 hom., cov: 32)
• Consequence: TRABD2B NM_001194986.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRABD2B	NM_001194986.2	c.1349+837A>G		intron_variant	Intron 6 of 6	ENST00000606738.3	NP_001181915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRABD2B	ENST00000606738.3	c.1349+837A>G		intron_variant	Intron 6 of 6	1	NM_001194986.2	ENSP00000476820.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66860 AN: 151930 Hom.: 15164 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.440 AC: 66902 AN: 152048 Hom.: 15172 Cov.: 32 AF XY: 0.435 AC XY: 32308 AN XY: 74310

African (AFR) AF: 0.355 AC: 14712 AN: 41442

American (AMR) AF: 0.350 AC: 5344 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1863 AN: 3468

East Asian (EAS) AF: 0.582 AC: 3004 AN: 5164

South Asian (SAS) AF: 0.378 AC: 1819 AN: 4814

European-Finnish (FIN) AF: 0.457 AC: 4840 AN: 10586

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33913 AN: 67966

Other (OTH) AF: 0.451 AC: 953 AN: 2114

Alfa AF: 0.474 Hom.: 47377

Bravo AF: 0.429

Asia WGS AF: 0.482 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.5
DANN	Benign	0.78
PhyloP100		0.13
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: rs2282361; hg19: chr1-48240005; COSMIC: COSV71108318; COSMIC: COSV71108318;