3-133616943-C-A

Position:

• chr3-133616943-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007027.4(TOPBP1):​c.3760-18G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TOPBP1 NM_007027.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.817

Genes affected

TOPBP1 (HGNC:17008): (DNA topoisomerase II binding protein 1) This gene encodes a binding protein which interacts with the C-terminal region of topoisomerase II beta. This interaction suggests a supportive role for this protein in the catalytic reactions of topoisomerase II beta through transient breakages of DNA strands. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPBP1	NM_007027.4	c.3760-18G>T		intron_variant		ENST00000260810.10	NP_008958.2
TOPBP1	NM_001363889.2	c.3745-18G>T		intron_variant			NP_001350818.1
TOPBP1	XM_017005636.3	c.3760-18G>T		intron_variant			XP_016861125.1
TOPBP1	XM_047447355.1	c.3745-18G>T		intron_variant			XP_047303311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPBP1	ENST00000260810.10	c.3760-18G>T		intron_variant		1	NM_007027.4	ENSP00000260810	P4
TOPBP1	ENST00000642236.1	c.3745-18G>T		intron_variant				ENSP00000493612	A2
TOPBP1	ENST00000505804.1	n.368-18G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 19

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.58

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: rs3732574; hg19: chr3-133335787;