10-43490979-T-C

Variant names:

• chr10-43490979-T-C
• rs3124205
• XR_007061981.1:n.2083-393T>C

Variant summary

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

The XR_007061981.1(ZNF487):​n.2083-393T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 133,520 control chromosomes in the GnomAD database, including 17,938 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 0.50 (17938 hom., cov: 23)
• Consequence: ZNF487 XR_007061981.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 1 publications found

Genes affected

ZNF487 (HGNC:23488): (zinc finger protein 487) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF487	XR_007061981.1	n.2083-393T>C		intron_variant	Intron 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.498 AC: 66481 AN: 133450 Hom.: 17928 Cov.: 23

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.498 AC: 66490 AN: 133520 Hom.: 17938 Cov.: 23 AF XY: 0.499 AC XY: 32185 AN XY: 64452

African (AFR) AF: 0.222 AC: 7383 AN: 33308

American (AMR) AF: 0.612 AC: 8375 AN: 13682

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1603 AN: 3322

East Asian (EAS) AF: 0.732 AC: 3387 AN: 4630

South Asian (SAS) AF: 0.509 AC: 2184 AN: 4290

European-Finnish (FIN) AF: 0.579 AC: 4521 AN: 7814

Middle Eastern (MID) AF: 0.548 AC: 136 AN: 248

European-Non Finnish (NFE) AF: 0.587 AC: 37255 AN: 63474

Other (OTH) AF: 0.542 AC: 1007 AN: 1858

Alfa AF: 0.477 Hom.: 1784

Bravo AF: 0.462

Asia WGS AF: 0.551 AC: 1825 AN: 3308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.8
DANN	Benign	0.49
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3124205; hg19: chr10-43986427;