1-47855549-C-T

Variant names:

• chr1-47855549-C-T
• rs946836
• NM_001194986.2:c.667-53930G>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.667-53930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,166 control chromosomes in the GnomAD database, including 9,837 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 0.36 (9837 hom., cov: 34)
• Consequence: TRABD2B NM_001194986.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001194986.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRABD2B	NM_001194986.2	MANE Select	c.667-53930G>A		intron	N/A	NP_001181915.1	A6NFA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRABD2B	ENST00000606738.3	TSL:1 MANE Select	c.667-53930G>A		intron	N/A	ENSP00000476820.1	A6NFA1
	TRABD2B	ENST00000878673.1		c.667-53930G>A		intron	N/A	ENSP00000548732.1
	TRABD2B	ENST00000878672.1		c.667-60789G>A		intron	N/A	ENSP00000548731.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54243 AN: 152050 Hom.: 9824 Cov.: 34

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.357 AC: 54307 AN: 152166 Hom.: 9837 Cov.: 34 AF XY: 0.356 AC XY: 26515 AN XY: 74382

African (AFR) AF: 0.392 AC: 16279 AN: 41494

American (AMR) AF: 0.364 AC: 5556 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3464

East Asian (EAS) AF: 0.494 AC: 2563 AN: 5184

South Asian (SAS) AF: 0.284 AC: 1371 AN: 4826

European-Finnish (FIN) AF: 0.377 AC: 3993 AN: 10586

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22282 AN: 68010

Other (OTH) AF: 0.351 AC: 741 AN: 2112

Alfa AF: 0.331 Hom.: 14268

Bravo AF: 0.358

Asia WGS AF: 0.398 AC: 1381 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	11
DANN	Benign	0.73
PhyloP100		0.16
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: rs946836; hg19: chr1-48321221;