6-27456405-T-C

Position:

• chr6-27456405-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF184	NM_001318891.2	c.298+421A>G		intron_variant		ENST00000683788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF184	ENST00000683788.1	c.298+421A>G		intron_variant			NM_001318891.2	P1
ZNF184	ENST00000211936.10	c.298+421A>G		intron_variant		1		P1
	ENST00000648356.1	n.732-311T>C		intron_variant, non_coding_transcript_variant
ZNF184	ENST00000377419.1	c.298+421A>G		intron_variant		4		P1

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

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.644

Alfa AF: 0.640 Hom.: 30337

Bravo AF: 0.607

Asia WGS AF: 0.657 AC: 2283 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	0.19
DANN	Benign	0.31

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: rs2092121; hg19: chr6-27424184;