rs888580

Variant names:

• chr8-264809-T-C
• rs888580
• XR_245320.4:n.392+614A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-264809-T-C
• chr8-264809-T-G

Variant summary

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

The XR_245320.4(LOC101927566):​n.392+614A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,138 control chromosomes in the GnomAD database, including 34,110 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 0.66 (34110 hom., cov: 34)
  • Failed GnomAD Quality Control
• Consequence: LOC101927566 XR_245320.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

Genes affected

LOC101927566 (HGNC:):

ZNF596 (HGNC:27268): (zinc finger protein 596) 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. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927566	XR_245320.4	n.392+614A>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF596	ENST00000640035.1	c.*636T>C		downstream_gene_variant		5		ENSP00000491031.1
ENSG00000254104	ENST00000522979.2	n.*137T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101030 AN: 152020 Hom.: 34065 Cov.: 34

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.665 AC: 101139 AN: 152138 Hom.: 34110 Cov.: 34 AF XY: 0.663 AC XY: 49319 AN XY: 74380

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.664

Alfa AF: 0.602 Hom.: 3635

Bravo AF: 0.679

Asia WGS AF: 0.654 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs888580; hg19: chr8-214809;