chr2-184933777-A-C

Position:

• chr2-184933777-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.386+44A>C		intron_variant		ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7	c.386+44A>C		intron_variant		1	NM_194250.2	ENSP00000303252	P1

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

GnomAD3 exomes AF: 0.593 AC: 128847 AN: 217170 Hom.: 40534 AF XY: 0.593 AC XY: 70129 AN XY: 118290

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 SAS exome AF: 0.548

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

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.709

Gnomad4 ASJ exome AF: 0.610

Gnomad4 EAS exome AF: 0.829

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.560

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.499

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.50

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: rs4667000; hg19: chr2-185798504;