4-1722852-C-T

Variant names:

• chr4-1722852-C-T
• rs1374468
• NM_006342.3:c.-1-569C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006342.3(TACC3):​c.-1-569C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,130 control chromosomes in the GnomAD database, including 2,747 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 0.18 (2747 hom., cov: 32)
• Consequence: TACC3 NM_006342.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

Genes affected

TACC3 (HGNC:11524): (transforming acidic coiled-coil containing protein 3) This gene encodes a member of the transforming acidic colied-coil protein family. The encoded protein is a motor spindle protein that may play a role in stabilization of the mitotic spindle. This protein may also play a role in growth a differentiation of certain cancer cells. [provided by RefSeq, Nov 2011]

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 (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACC3	NM_006342.3	c.-1-569C>T		intron_variant	Intron 1 of 15	ENST00000313288.9	NP_006333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACC3	ENST00000313288.9	c.-1-569C>T		intron_variant	Intron 1 of 15	1	NM_006342.3	ENSP00000326550.4

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27526 AN: 152014 Hom.: 2735 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.181 AC: 27574 AN: 152130 Hom.: 2747 Cov.: 32 AF XY: 0.176 AC XY: 13093 AN XY: 74388

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0860

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.181

Alfa AF: 0.192 Hom.: 4277

Bravo AF: 0.186

Asia WGS AF: 0.0980 AC: 339 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	2.6
DANN	Benign	0.45

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: rs1374468; hg19: chr4-1724579;