chr1-247051576-A-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF670	NM_033213.5	c.4-12039T>G		intron_variant	Intron 1 of 3	ENST00000366503.3	NP_149990.1
ZNF670	NM_001204220.2	c.4-12039T>G		intron_variant	Intron 1 of 3		NP_001191149.1
ZNF670-ZNF695	NR_037894.2	n.218+27018T>G		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF670	ENST00000366503.3	c.4-12039T>G		intron_variant	Intron 1 of 3	1	NM_033213.5	ENSP00000355459.2
ZNF670-ZNF695	ENST00000465049.6	n.3+27018T>G		intron_variant	Intron 1 of 6	5		ENSP00000428213.1
ZNF670-ZNF695	ENST00000474541.1	n.3+27018T>G		intron_variant	Intron 1 of 5	2		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

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.00753

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.318

Alfa AF: 0.244 Hom.: 780

Bravo AF: 0.327

Asia WGS AF: 0.145 AC: 509 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.0
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs4925540; hg19: chr1-247214878;