rs4925540

Variant names:

• chr1-247051576-A-C
• rs4925540
• NM_033213.5:c.4-12039T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-247051576-A-C
• chr1-247051576-A-T

Variant summary

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

The NM_033213.5(ZNF670):​c.4-12039T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,906 control chromosomes in the GnomAD database, including 8,889 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 0.33 (8889 hom., cov: 31)
• Consequence: ZNF670 NM_033213.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 10 publications found

Genes affected

ZNF670 (HGNC:28167): (zinc finger protein 670) 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]

ZNF670-ZNF695 (HGNC:49200): (ZNF670-ZNF695 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 670 (ZNF670) and zinc finger protein 695 (ZNF695) genes on chromosome 1. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF670	NM_033213.5	MANE Select	c.4-12039T>G		intron	N/A	NP_149990.1
	ZNF670	NM_001204220.2		c.4-12039T>G		intron	N/A	NP_001191149.1
	ZNF670-ZNF695	NR_037894.2		n.218+27018T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF670	ENST00000366503.3	TSL:1 MANE Select	c.4-12039T>G		intron	N/A	ENSP00000355459.2
	ZNF670-ZNF695	ENST00000465049.6	TSL:5	n.3+27018T>G		intron	N/A	ENSP00000428213.1
	ZNF670-ZNF695	ENST00000474541.1	TSL:2	n.3+27018T>G		intron	N/A	ENSP00000428036.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49502 AN: 151788 Hom.: 8881 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.326 AC: 49523 AN: 151906 Hom.: 8889 Cov.: 31 AF XY: 0.319 AC XY: 23691 AN XY: 74240

African (AFR) AF: 0.456 AC: 18889 AN: 41392

American (AMR) AF: 0.239 AC: 3644 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1007 AN: 3464

East Asian (EAS) AF: 0.00753 AC: 39 AN: 5176

South Asian (SAS) AF: 0.280 AC: 1347 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2751 AN: 10516

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20758 AN: 67958

Other (OTH) AF: 0.318 AC: 670 AN: 2110

Alfa AF: 0.305 Hom.: 11069

Bravo AF: 0.327

Asia WGS AF: 0.145 AC: 509 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.0
DANN	Benign	0.44
PhyloP100		0.13
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: rs4925540; hg19: chr1-247214878;