rs10957985

Variant names:

• chr8-80877686-G-A
• rs10957985
• XM_017013725.2:c.3+6473C>T

Variant summary

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

The XM_017013725.2(ZNF704):​c.3+6473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,048 control chromosomes in the GnomAD database, including 11,082 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 0.35 (11082 hom., cov: 32)
• Consequence: ZNF704 XM_017013725.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF704	XM_017013725.2	c.3+6473C>T		intron_variant	Intron 1 of 8		XP_016869214.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53472 AN: 151930 Hom.: 11084 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.352 AC: 53473 AN: 152048 Hom.: 11082 Cov.: 32 AF XY: 0.354 AC XY: 26327 AN XY: 74308

African (AFR) AF: 0.128 AC: 5291 AN: 41490

American (AMR) AF: 0.503 AC: 7689 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3466

East Asian (EAS) AF: 0.361 AC: 1863 AN: 5162

South Asian (SAS) AF: 0.347 AC: 1672 AN: 4818

European-Finnish (FIN) AF: 0.428 AC: 4516 AN: 10544

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29626 AN: 67970

Other (OTH) AF: 0.389 AC: 823 AN: 2114

Alfa AF: 0.407 Hom.: 24821

Bravo AF: 0.350

Asia WGS AF: 0.355 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.68
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs10957985; hg19: chr8-81789921;