rs7018449

chr8-80664730-T-Cchr8-80664730-T-G

Variant summary

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

The NM_001033723.3(ZNF704):c.927+85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 1,535,786 control chromosomes in the GnomAD database, including 8,639 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 0.15 (3359 hom., cov: 32)
  • Exomes 𝑓: 0.068 (5280 hom.)
• Consequence: ZNF704 NM_001033723.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

Genes affected

ZNF704 (HGNC:32291): (zinc finger protein 704) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF704	NM_001033723.3	c.927+85A>G		intron_variant		ENST00000327835.7
ZNF704	NM_001367783.1	c.1449+85A>G		intron_variant
ZNF704	XM_017013725.2	c.951+85A>G		intron_variant
ZNF704	XR_928797.3	n.1873+85A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF704	ENST00000327835.7	c.927+85A>G		intron_variant		1	NM_001033723.3	P1
ZNF704	ENST00000519936.2	c.1449+85A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23097 AN: 152096 Hom.: 3340 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0822

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.0680 AC: 94054 AN: 1383574 Hom.: 5280 AF XY: 0.0659 AC XY: 45284 AN XY: 686966

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.0560

Gnomad4 ASJ exome AF: 0.0908

Gnomad4 EAS exome AF: 0.000358

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.0583

Gnomad4 NFE exome AF: 0.0642

Gnomad4 OTH exome AF: 0.0804

GnomAD4 genome AF: 0.152 AC: 23157 AN: 152212 Hom.: 3359 Cov.: 32 AF XY: 0.147 AC XY: 10964 AN XY: 74420

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.0986

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.0661

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0716 Hom.: 1202

Bravo AF: 0.162

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.026
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7018449; hg19: chr8-81576965;