chr8-80723736-C-T

Variant names:

• chr8-80723736-C-T
• rs6992620
• NM_001033723.3:c.222-30629G>A

Variant summary

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

The NM_001033723.3(ZNF704):​c.222-30629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,002 control chromosomes in the GnomAD database, including 4,688 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 (4688 hom., cov: 32)
• Consequence: ZNF704 NM_001033723.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF704	NM_001033723.3	c.222-30629G>A		intron_variant	Intron 2 of 8	ENST00000327835.7	NP_001028895.1
ZNF704	NM_001367783.1	c.744-30629G>A		intron_variant	Intron 2 of 8		NP_001354712.1
ZNF704	XM_017013725.2	c.246-30629G>A		intron_variant	Intron 2 of 8		XP_016869214.1
ZNF704	XR_928797.3	n.1168-30629G>A		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF704	ENST00000327835.7	c.222-30629G>A		intron_variant	Intron 2 of 8	1	NM_001033723.3	ENSP00000331462.3
ZNF704	ENST00000519936.2	c.744-30629G>A		intron_variant	Intron 2 of 8	5		ENSP00000427715.2
ZNF704	ENST00000520336.1	n.149-29428G>A		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26402 AN: 151884 Hom.: 4667 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.0886

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0613

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.174 AC: 26459 AN: 152002 Hom.: 4688 Cov.: 32 AF XY: 0.169 AC XY: 12556 AN XY: 74298

African (AFR) AF: 0.456 AC: 18890 AN: 41404

American (AMR) AF: 0.0897 AC: 1369 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0886 AC: 307 AN: 3466

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0213 AC: 103 AN: 4828

European-Finnish (FIN) AF: 0.0613 AC: 647 AN: 10562

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0693 AC: 4712 AN: 67980

Other (OTH) AF: 0.149 AC: 314 AN: 2114

Alfa AF: 0.0712 Hom.: 454

Bravo AF: 0.187

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.4
DANN	Benign	0.66
PhyloP100		0.12
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: rs6992620; hg19: chr8-81635971;