rs7248493

Variant names:

• chr19-58199741-C-G
• rs7248493
• NM_133502.3:c.257-6979C>G

Variant summary

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

The NM_133502.3(ZNF274):​c.257-6979C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,140 control chromosomes in the GnomAD database, including 2,812 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 0.19 (2812 hom., cov: 33)
• Consequence: ZNF274 NM_133502.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 10 publications found

Genes affected

ZNF274 (HGNC:13068): (zinc finger protein 274) This gene encodes a zinc finger protein containing five C2H2-type zinc finger domains, one or two Kruppel-associated box A (KRAB A) domains, and a leucine-rich domain. The encoded protein has been suggested to be a transcriptional repressor. It localizes predominantly to the nucleolus. Alternatively spliced transcript variants encoding different isoforms exist. These variants utilize alternative polyadenylation signals. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133502.3. 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
	ZNF274	NM_133502.3	MANE Select	c.257-6979C>G		intron	N/A	NP_598009.1	Q96GC6-1
	ZNF274	NM_016325.4		c.161-6979C>G		intron	N/A	NP_057409.1	Q96GC6-2
	ZNF274	NM_001278734.2		c.131-6979C>G		intron	N/A	NP_001265663.1	A0A0A0MR47

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF274	ENST00000617501.5	TSL:1 MANE Select	c.257-6979C>G		intron	N/A	ENSP00000484810.1	Q96GC6-1
	ZNF274	ENST00000345813.7	TSL:1	c.161-6979C>G		intron	N/A	ENSP00000321187.5	Q96GC6-2
	ZNF274	ENST00000326804.8	TSL:1	c.131-6979C>G		intron	N/A	ENSP00000321209.5	A0A0A0MR47

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28447 AN: 152022 Hom.: 2810 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.187 AC: 28462 AN: 152140 Hom.: 2812 Cov.: 33 AF XY: 0.183 AC XY: 13608 AN XY: 74372

African (AFR) AF: 0.197 AC: 8193 AN: 41508

American (AMR) AF: 0.153 AC: 2345 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3470

East Asian (EAS) AF: 0.0204 AC: 106 AN: 5184

South Asian (SAS) AF: 0.107 AC: 515 AN: 4824

European-Finnish (FIN) AF: 0.188 AC: 1983 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13951 AN: 67970

Other (OTH) AF: 0.205 AC: 433 AN: 2110

Alfa AF: 0.199 Hom.: 408

Bravo AF: 0.185

Asia WGS AF: 0.0940 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.57
PhyloP100		0.31
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: rs7248493; hg19: chr19-58711108;