6-27456405-T-C

Variant names:

• chr6-27456405-T-C
• rs2092121
• NM_001318891.2:c.298+421A>G

Variant summary

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

The NM_001318891.2(ZNF184):​c.298+421A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,998 control chromosomes in the GnomAD database, including 27,775 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 0.60 (27775 hom., cov: 32)
• Consequence: ZNF184 NM_001318891.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.25
• Publications: 7 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]

ENSG00000285849 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318891.2. 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
	ZNF184	NM_001318891.2	MANE Select	c.298+421A>G		intron	N/A	NP_001305820.1	Q99676
	ZNF184	NM_001318892.2		c.298+421A>G		intron	N/A	NP_001305821.1	Q99676
	ZNF184	NM_007149.3		c.298+421A>G		intron	N/A	NP_009080.2	Q99676

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF184	ENST00000683788.1	MANE Select	c.298+421A>G		intron	N/A	ENSP00000508298.1	Q99676
	ZNF184	ENST00000211936.10	TSL:1	c.298+421A>G		intron	N/A	ENSP00000211936.6	Q99676
	ZNF184	ENST00000377419.1	TSL:4	c.298+421A>G		intron	N/A	ENSP00000366636.1	Q99676

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91676 AN: 151880 Hom.: 27771 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.603 AC: 91715 AN: 151998 Hom.: 27775 Cov.: 32 AF XY: 0.604 AC XY: 44856 AN XY: 74264

African (AFR) AF: 0.527 AC: 21821 AN: 41426

American (AMR) AF: 0.656 AC: 10027 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2712 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2963 AN: 5174

South Asian (SAS) AF: 0.722 AC: 3482 AN: 4822

European-Finnish (FIN) AF: 0.546 AC: 5760 AN: 10540

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42888 AN: 67966

Other (OTH) AF: 0.644 AC: 1359 AN: 2110

Alfa AF: 0.636 Hom.: 47200

Bravo AF: 0.607

Asia WGS AF: 0.657 AC: 2283 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	0.19
DANN	Benign	0.31
PhyloP100		-4.2
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: rs2092121; hg19: chr6-27424184;