1-47970476-T-C

Position:

• chr1-47970476-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.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

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=-0.88).
• 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/exons	MANE	UniProt
TRABD2B	NM_001194986.2	c.666+23558A>G		intron_variant		ENST00000606738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRABD2B	ENST00000606738.3	c.666+23558A>G		intron_variant		1	NM_001194986.2	P1
TRABD2B	ENST00000435576.2	n.179+23558A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.250

Alfa AF: 0.247 Hom.: 716

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

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: rs12080929; hg19: chr1-48436148;