rs11208363

Variant names:

• chr1-40544782-A-G
• rs11208363
• NM_152373.4:c.239-1780A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF684	NM_152373.4	MANE Select	c.239-1780A>G		intron	N/A	NP_689586.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF684	ENST00000372699.8	TSL:1 MANE Select	c.239-1780A>G		intron	N/A	ENSP00000361784.3
	ZNF684	ENST00000372697.7	TSL:3	c.*264A>G		3_prime_UTR	Exon 5 of 5	ENSP00000361782.3
	ZNF684	ENST00000372696.3	TSL:3	c.*326A>G		3_prime_UTR	Exon 5 of 5	ENSP00000361781.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.396 AC: 19 AN: 48

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.210 AC: 13 AN: 62

European-Finnish (FIN) AF: 0.143 AC: 2 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.155 AC: 40 AN: 258

Other (OTH) AF: 0.150 AC: 3 AN: 20

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

African (AFR) AF: 0.376 AC: 15590 AN: 41476

American (AMR) AF: 0.343 AC: 5241 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2802 AN: 5184

South Asian (SAS) AF: 0.352 AC: 1695 AN: 4820

European-Finnish (FIN) AF: 0.144 AC: 1530 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9428 AN: 68020

Other (OTH) AF: 0.224 AC: 474 AN: 2114

Alfa AF: 0.179 Hom.: 13875

Bravo AF: 0.269

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		1.2
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: rs11208363; hg19: chr1-41010454;