rs7105512

Positions:

• chr11-113748617-G-T

Variant summary

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

The NM_004724.4(ZW10):​c.926-197C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 151,976 control chromosomes in the GnomAD database, including 2,399 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 0.17 (2399 hom., cov: 32)
• Consequence: ZW10 NM_004724.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

ZW10 (HGNC:13194): (zw10 kinetochore protein) This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. This protein is an essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZW10	NM_004724.4	c.926-197C>A		intron_variant		ENST00000200135.8	NP_004715.1
ZW10	XM_017018558.3	c.734-197C>A		intron_variant			XP_016874047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZW10	ENST00000200135.8	c.926-197C>A		intron_variant		1	NM_004724.4	ENSP00000200135.3
ZW10	ENST00000535142.5	n.926-197C>A		intron_variant		2		ENSP00000440879.1
ZW10	ENST00000538209.1	n.*178-197C>A		intron_variant		3		ENSP00000439197.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26500 AN: 151856 Hom.: 2394 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.175 AC: 26541 AN: 151976 Hom.: 2399 Cov.: 32 AF XY: 0.174 AC XY: 12942 AN XY: 74302

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.187

Alfa AF: 0.176 Hom.: 1232

Bravo AF: 0.173

Asia WGS AF: 0.139 AC: 484 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.72

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: rs7105512; hg19: chr11-113619339;