rs8073471

Positions:

• chr17-82939616-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005993.5(TBCD):​c.3479+140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 688,292 control chromosomes in the GnomAD database, including 7,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1221 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6341 hom.)
• Consequence: TBCD NM_005993.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.705

Genes affected

TBCD (HGNC:11581): (tubulin folding cofactor D) Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]

TBCD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 17-82939616-A-G is Benign according to our data. Variant chr17-82939616-A-G is described in ClinVar as [Benign]. Clinvar id is 1278100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBCD	NM_005993.5	c.3479+140A>G		intron_variant		ENST00000355528.9	NP_005984.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBCD	ENST00000355528.9	c.3479+140A>G		intron_variant		1	NM_005993.5	ENSP00000347719.4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18459 AN: 152018 Hom.: 1222 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.144 AC: 77112 AN: 536156 Hom.: 6341 AF XY: 0.150 AC XY: 42301 AN XY: 281840

Gnomad4 AFR exome AF: 0.0936

Gnomad4 AMR exome AF: 0.0726

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.0977

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.121 AC: 18467 AN: 152136 Hom.: 1221 Cov.: 32 AF XY: 0.121 AC XY: 9030 AN XY: 74396

Gnomad4 AFR AF: 0.0952

Gnomad4 AMR AF: 0.0878

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.0783

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.128

Alfa AF: 0.141 Hom.: 751

Bravo AF: 0.116

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.38

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: rs8073471; hg19: chr17-80897492;