rs12940887

Variant names:

• chr17-49325445-C-T
• rs12940887
• NM_001145365.3:c.-258-7462G>A

Variant summary

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

The NM_001145365.3(ZNF652):​c.-258-7462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,074 control chromosomes in the GnomAD database, including 7,002 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 0.27 (7002 hom., cov: 31)
• Consequence: ZNF652 NM_001145365.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 67 publications found

Genes affected

ZNF652 (HGNC:29147): (zinc finger protein 652) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active 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 (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF652	NM_001145365.3	c.-258-7462G>A		intron_variant	Intron 1 of 5	ENST00000430262.3	NP_001138837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF652	ENST00000430262.3	c.-258-7462G>A		intron_variant	Intron 1 of 5	1	NM_001145365.3	ENSP00000416305.2
ZNF652	ENST00000362063.6	c.-258-7462G>A		intron_variant	Intron 1 of 5	1		ENSP00000354686.2
ZNF652	ENST00000508237.5	n.-382-2937G>A		intron_variant	Intron 1 of 7	2		ENSP00000424848.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41721 AN: 151956 Hom.: 6997 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.274 AC: 41722 AN: 152074 Hom.: 7002 Cov.: 31 AF XY: 0.271 AC XY: 20120 AN XY: 74292

African (AFR) AF: 0.101 AC: 4194 AN: 41522

American (AMR) AF: 0.235 AC: 3588 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1143 AN: 5180

South Asian (SAS) AF: 0.159 AC: 764 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4523 AN: 10510

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25778 AN: 67982

Other (OTH) AF: 0.283 AC: 597 AN: 2110

Alfa AF: 0.318 Hom.: 12709

Bravo AF: 0.256

Asia WGS AF: 0.152 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.32
PhyloP100		0.17
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: rs12940887; hg19: chr17-47402807;