rs4930390

Variant names:

• chr11-66792552-A-G
• rs4930390
• NM_001302084.2:c.136-3729A>G

Variant summary

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

The NM_001302084.2(TOP6BL):​c.136-3729A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,114 control chromosomes in the GnomAD database, including 4,442 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 (4442 hom., cov: 32)
• Consequence: TOP6BL NM_001302084.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 16 publications found

Genes affected

TOP6BL (HGNC:26197): (TOP6B like initiator of meiotic double strand breaks) Predicted to be involved in meiotic DNA double-strand break formation and reciprocal meiotic recombination. Predicted to be located in chromosome. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TOP6BL Gene-Disease associations (from GenCC):

• hydatidiform mole, recurrent, 4

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302084.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOP6BL	NM_001302084.2	MANE Select	c.136-3729A>G		intron	N/A	NP_001289013.1
	TOP6BL	NM_024650.4		c.487-3729A>G		intron	N/A	NP_078926.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOP6BL	ENST00000540737.7	TSL:2 MANE Select	c.136-3729A>G		intron	N/A	ENSP00000444319.1
	TOP6BL	ENST00000525449.6	TSL:1	c.169-3729A>G		intron	N/A	ENSP00000434648.2
	TOP6BL	ENST00000525908.6	TSL:2	c.487-3729A>G		intron	N/A	ENSP00000432039.3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36517 AN: 151996 Hom.: 4445 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.240 AC: 36516 AN: 152114 Hom.: 4442 Cov.: 32 AF XY: 0.238 AC XY: 17721 AN XY: 74358

African (AFR) AF: 0.229 AC: 9521 AN: 41516

American (AMR) AF: 0.209 AC: 3189 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3468

East Asian (EAS) AF: 0.161 AC: 831 AN: 5170

South Asian (SAS) AF: 0.140 AC: 677 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2805 AN: 10570

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17593 AN: 67974

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.257 Hom.: 16462

Bravo AF: 0.238

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.65
PhyloP100		0.24
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: rs4930390; hg19: chr11-66560023;