chr1-47774333-T-C

Position:

• chr1-47774333-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TRABD2B	NM_001194986.2	c.1349+837A>G		intron_variant		ENST00000606738.3	NP_001181915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRABD2B	ENST00000606738.3	c.1349+837A>G		intron_variant		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

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.451

Alfa AF: 0.486 Hom.: 30634

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2282361; hg19: chr1-48240005; COSMIC: COSV71108318; COSMIC: COSV71108318;