chr17-49345001-G-A

Variant names:

• chr17-49345001-G-A
• rs11652146
• NM_001145365.3:c.-259+16908C>T

Variant summary

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

The NM_001145365.3(ZNF652):​c.-259+16908C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,974 control chromosomes in the GnomAD database, including 34,301 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 0.67 (34301 hom., cov: 30)
• Consequence: ZNF652 NM_001145365.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251
• Publications: 17 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF652	NM_001145365.3	c.-259+16908C>T		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.-259+16908C>T		intron_variant	Intron 1 of 5	1	NM_001145365.3	ENSP00000416305.2
ZNF652	ENST00000362063.6	c.-259+17412C>T		intron_variant	Intron 1 of 5	1		ENSP00000354686.2
ZNF652	ENST00000508237.5	n.-383+16908C>T		intron_variant	Intron 1 of 7	2		ENSP00000424848.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101701 AN: 151856 Hom.: 34290 Cov.: 30

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.670 AC: 101761 AN: 151974 Hom.: 34301 Cov.: 30 AF XY: 0.667 AC XY: 49560 AN XY: 74278

African (AFR) AF: 0.634 AC: 26261 AN: 41430

American (AMR) AF: 0.640 AC: 9779 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1996 AN: 3468

East Asian (EAS) AF: 0.695 AC: 3590 AN: 5164

South Asian (SAS) AF: 0.576 AC: 2779 AN: 4826

European-Finnish (FIN) AF: 0.729 AC: 7679 AN: 10536

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47492 AN: 67966

Other (OTH) AF: 0.679 AC: 1433 AN: 2112

Alfa AF: 0.675 Hom.: 17556

Bravo AF: 0.662

Asia WGS AF: 0.676 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.16
DANN	Benign	0.46
PhyloP100		-0.25
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: rs11652146; hg19: chr17-47422363;