rs10487289

Variant names:

• chr7-112268871-A-G
• rs10487289
• NM_021994.3:c.92-18002A>G

Variant summary

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

The NM_021994.3(ZNF277):​c.92-18002A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 152,224 control chromosomes in the GnomAD database, including 641 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 0.056 (641 hom., cov: 32)
• Consequence: ZNF277 NM_021994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696
• Publications: 2 publications found

Genes affected

ZNF277 (HGNC:13070): (zinc finger protein 277) Predicted to enable RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and metal ion binding activity. Predicted to act upstream of or within cellular response to hydrogen peroxide and regulation of cellular senescence. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF277	NM_021994.3	c.92-18002A>G		intron_variant	Intron 1 of 11	ENST00000361822.8	NP_068834.2
ZNF277	XM_011515768.4	c.-139-18006A>G		intron_variant	Intron 1 of 11		XP_011514070.1
ZNF277	XM_017011720.3	c.-170-18006A>G		intron_variant	Intron 1 of 10		XP_016867209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF277	ENST00000361822.8	c.92-18002A>G		intron_variant	Intron 1 of 11	1	NM_021994.3	ENSP00000354501.3

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8532 AN: 152106 Hom.: 636 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00972

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0562 AC: 8561 AN: 152224 Hom.: 641 Cov.: 32 AF XY: 0.0541 AC XY: 4029 AN XY: 74426

African (AFR) AF: 0.172 AC: 7143 AN: 41516

American (AMR) AF: 0.0256 AC: 391 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0238 AC: 115 AN: 4822

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00971 AC: 660 AN: 68004

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0425 Hom.: 79

Bravo AF: 0.0621

Asia WGS AF: 0.0200 AC: 70 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
DANN	Benign	0.82
PhyloP100		0.70
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: rs10487289; hg19: chr7-111908926;