6-27446145-A-G

Variant names:

• chr6-27446145-A-G
• rs13195040
• NR_144687.2:n.570+10681T>C

Variant summary

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

The NR_144687.2(ZNF184):​n.570+10681T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0861 in 152,312 control chromosomes in the GnomAD database, including 709 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 0.086 (709 hom., cov: 32)
• Consequence: ZNF184 NR_144687.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656
• Publications: 37 publications found

Genes affected

ZNF184 (HGNC:12975): (zinc finger protein 184) The protein encoded by this gene is predicted to be a Kruppel C2H2-type zinc-finger protein family member. Sequence analysis predicts that the protein contains two Kruppel associated box (KRAB) boxes in the N-terminus and highly conserved zinc finger motifs at the C-terminus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_144687.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF184	NR_144687.2		n.570+10681T>C		intron	N/A
	ZNF184	NR_144688.2		n.570+10681T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13117 AN: 152194 Hom.: 710 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0717

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

GnomAD4 genome AF: 0.0861 AC: 13121 AN: 152312 Hom.: 709 Cov.: 32 AF XY: 0.0804 AC XY: 5990 AN XY: 74482

African (AFR) AF: 0.135 AC: 5616 AN: 41552

American (AMR) AF: 0.0568 AC: 869 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3470

East Asian (EAS) AF: 0.00404 AC: 21 AN: 5192

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4828

European-Finnish (FIN) AF: 0.0379 AC: 402 AN: 10620

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5827 AN: 68020

Other (OTH) AF: 0.0710 AC: 150 AN: 2114

Alfa AF: 0.0893 Hom.: 1318

Bravo AF: 0.0916

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.3
DANN	Benign	0.86
PhyloP100		-0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13195040; hg19: chr6-27413924;