rs7260598

Variant names:

• chr19-24039984-A-G
• rs7260598
• NM_001278661.2:c.-189-6200A>G

Variant summary

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

The NM_001278661.2(ZNF254):​c.-189-6200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,196 control chromosomes in the GnomAD database, including 1,914 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 0.16 (1914 hom., cov: 33)
• Consequence: ZNF254 NM_001278661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 6 publications found

Genes affected

ZNF254 (HGNC:13047): (zinc finger protein 254) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See ZFP93 (MIM 604749) for additional information on zinc finger proteins.[supplied by OMIM, Jul 2002]

ENSG00000268362 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF254	NM_001278661.2	c.-189-6200A>G		intron_variant	Intron 1 of 4		NP_001265590.1
ZNF254	NM_001278677.2	c.-261-6200A>G		intron_variant	Intron 1 of 5		NP_001265606.1
ZNF254	NM_001278663.2	c.-98-6200A>G		intron_variant	Intron 1 of 2		NP_001265592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF254	ENST00000613065.4	c.-189-6200A>G		intron_variant	Intron 1 of 4	3		ENSP00000482703.1
ENSG00000268362	ENST00000594934.6	n.199-6200A>G		intron_variant	Intron 1 of 3	2
ENSG00000268362	ENST00000597683.1	n.174-6200A>G		intron_variant	Intron 1 of 6	2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23939 AN: 152078 Hom.: 1909 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.157 AC: 23963 AN: 152196 Hom.: 1914 Cov.: 33 AF XY: 0.156 AC XY: 11644 AN XY: 74408

African (AFR) AF: 0.163 AC: 6769 AN: 41522

American (AMR) AF: 0.112 AC: 1713 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3470

East Asian (EAS) AF: 0.175 AC: 907 AN: 5182

South Asian (SAS) AF: 0.153 AC: 739 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1934 AN: 10590

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11008 AN: 67992

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.158 Hom.: 7840

Bravo AF: 0.154

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.55
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7260598; hg19: chr19-24222786;