rs6698119

Variant names:

• chr1-47809315-A-G
• rs6698119
• NM_001194986.2:c.667-7696T>C

Variant summary

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

The NM_001194986.2(TRABD2B):​c.667-7696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,018 control chromosomes in the GnomAD database, including 8,258 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 0.32 (8258 hom., cov: 32)
• Consequence: TRABD2B NM_001194986.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRABD2B	NM_001194986.2	c.667-7696T>C		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.667-7696T>C		intron_variant	Intron 2 of 6	1	NM_001194986.2	ENSP00000476820.1
TRABD2B	ENST00000435576.2	n.180-7696T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48810 AN: 151900 Hom.: 8246 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.321 AC: 48843 AN: 152018 Hom.: 8258 Cov.: 32 AF XY: 0.326 AC XY: 24219 AN XY: 74278

African (AFR) AF: 0.258 AC: 10690 AN: 41444

American (AMR) AF: 0.350 AC: 5342 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3468

East Asian (EAS) AF: 0.184 AC: 952 AN: 5168

South Asian (SAS) AF: 0.541 AC: 2600 AN: 4806

European-Finnish (FIN) AF: 0.311 AC: 3286 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23475 AN: 67962

Other (OTH) AF: 0.342 AC: 721 AN: 2106

Alfa AF: 0.350 Hom.: 5110

Bravo AF: 0.316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.52
PhyloP100		-1.7
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: rs6698119; hg19: chr1-48274987;