2-184933777-A-C

Variant names:

• chr2-184933777-A-C
• rs4667000
• NM_194250.2:c.386+44A>C

Variant summary

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

The NM_194250.2(ZNF804A):​c.386+44A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,570,832 control chromosomes in the GnomAD database, including 266,487 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 0.47 (20642 hom., cov: 31)
  • Exomes 𝑓: 0.58 (245845 hom.)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 7 publications found

Genes affected

ZNF804A (HGNC:21711): (zinc finger protein 804A) The protein encoded by this gene is a zinc finger binding protein. Polymorphisms in this gene, especially rs1344706, are thought to confer increased susceptibility to schizophrenia, bipolar disorder, and heroin addiciton. [provided by RefSeq, Nov 2015]

ZNF804A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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 (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194250.2. 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
	ZNF804A	NM_194250.2	MANE Select	c.386+44A>C		intron	N/A	NP_919226.1	Q7Z570

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF804A	ENST00000302277.7	TSL:1 MANE Select	c.386+44A>C		intron	N/A	ENSP00000303252.6	Q7Z570

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71902 AN: 151706 Hom.: 20645 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.503

GnomAD2 exomes AF: 0.593 AC: 128847 AN: 217170 AF XY: 0.593

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.722

Gnomad ASJ exome AF: 0.619

Gnomad EAS exome AF: 0.841

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.581 AC: 824750 AN: 1419008 Hom.: 245845 Cov.: 26 AF XY: 0.581 AC XY: 409807 AN XY: 705684

African (AFR) AF: 0.111 AC: 3434 AN: 31048

American (AMR) AF: 0.709 AC: 24879 AN: 35112

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 15123 AN: 24790

East Asian (EAS) AF: 0.829 AC: 32005 AN: 38592

South Asian (SAS) AF: 0.547 AC: 43389 AN: 79282

European-Finnish (FIN) AF: 0.642 AC: 33474 AN: 52172

Middle Eastern (MID) AF: 0.417 AC: 2337 AN: 5602

European-Non Finnish (NFE) AF: 0.583 AC: 637354 AN: 1093964

Other (OTH) AF: 0.560 AC: 32755 AN: 58446

GnomAD4 genome AF: 0.474 AC: 71901 AN: 151824 Hom.: 20642 Cov.: 31 AF XY: 0.480 AC XY: 35591 AN XY: 74190

African (AFR) AF: 0.134 AC: 5533 AN: 41444

American (AMR) AF: 0.645 AC: 9819 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2105 AN: 3464

East Asian (EAS) AF: 0.820 AC: 4222 AN: 5150

South Asian (SAS) AF: 0.543 AC: 2615 AN: 4814

European-Finnish (FIN) AF: 0.628 AC: 6614 AN: 10526

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39387 AN: 67884

Other (OTH) AF: 0.499 AC: 1050 AN: 2106

Alfa AF: 0.465 Hom.: 2695

Bravo AF: 0.466

Asia WGS AF: 0.615 AC: 2139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.50
PhyloP100		-0.29
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: rs4667000; hg19: chr2-185798504;