rs11208363

chr1-40544782-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_152373.4(ZNF684):c.239-1780A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,596 control chromosomes in the GnomAD database, including 5,941 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 0.25 (5930 hom., cov: 33)
  • Exomes 𝑓: 0.19 (11 hom.)
• Consequence: ZNF684 NM_152373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

Genes affected

ZNF684 (HGNC:28418): (zinc finger protein 684) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within innate immune response and negative regulation of single stranded viral RNA replication via double stranded DNA intermediate. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF684	NM_152373.4	c.239-1780A>G		intron_variant		ENST00000372699.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF684	ENST00000372699.8	c.239-1780A>G		intron_variant		1	NM_152373.4	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37530 AN: 152068 Hom.: 5920 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.193 AC: 79 AN: 410 Hom.: 11 Cov.: 0 AF XY: 0.202 AC XY: 46 AN XY: 228

Gnomad4 AMR exome AF: 0.396

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.247 AC: 37600 AN: 152186 Hom.: 5930 Cov.: 33 AF XY: 0.250 AC XY: 18594 AN XY: 74408

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.224

Alfa AF: 0.167 Hom.: 5636

Bravo AF: 0.269

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	15
Dann	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs11208363; hg19: chr1-41010454;