NM_194250.2:c.112-25240T>C

Variant names:

• chr2-184841129-T-C
• rs7605689
• NM_194250.2:c.112-25240T>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.112-25240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,932 control chromosomes in the GnomAD database, including 10,564 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 0.32 (10564 hom., cov: 32)
• Consequence: ZNF804A NM_194250.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 6 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

ENSG00000299447 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF804A	NM_194250.2	c.112-25240T>C		intron_variant	Intron 1 of 3	ENST00000302277.7	NP_919226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF804A	ENST00000302277.7	c.112-25240T>C		intron_variant	Intron 1 of 3	1	NM_194250.2	ENSP00000303252.6
ENSG00000299447	ENST00000763602.1	n.51-753A>G		intron_variant	Intron 1 of 2
ENSG00000299447	ENST00000763603.1	n.72-753A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48548 AN: 151812 Hom.: 10527 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.320 AC: 48633 AN: 151932 Hom.: 10564 Cov.: 32 AF XY: 0.311 AC XY: 23080 AN XY: 74260

African (AFR) AF: 0.619 AC: 25607 AN: 41362

American (AMR) AF: 0.210 AC: 3196 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3466

East Asian (EAS) AF: 0.0433 AC: 224 AN: 5170

South Asian (SAS) AF: 0.143 AC: 688 AN: 4820

European-Finnish (FIN) AF: 0.130 AC: 1373 AN: 10592

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.230 AC: 15619 AN: 67956

Other (OTH) AF: 0.303 AC: 641 AN: 2116

Alfa AF: 0.264 Hom.: 860

Bravo AF: 0.339

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.16
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: rs7605689; hg19: chr2-185705856; COSMIC: COSV107394095;