rs999647

Positions:

• chr18-74859594-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017757.3(ZNF407):​c.4878-17603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,118 control chromosomes in the GnomAD database, including 18,324 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 0.46 (18324 hom., cov: 33)
• Consequence: ZNF407 NM_017757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

Genes affected

ZNF407 (HGNC:19904): (zinc finger protein 407) This gene encodes a zinc finger protein whose exact function is not known. It may be involved in transcriptional regulation. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.4878-17603A>G		intron_variant		ENST00000299687.10	NP_060227.2
ZNF407	NM_001146189.1	c.4878-17603A>G		intron_variant			NP_001139661.1
ZNF407	NM_001384475.1	c.4878-17603A>G		intron_variant			NP_001371404.1
ZNF407	XM_017025838.3	c.4878-17603A>G		intron_variant			XP_016881327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.4878-17603A>G		intron_variant		1	NM_017757.3	ENSP00000299687	P2
ZNF407	ENST00000577538.5	c.4878-17603A>G		intron_variant		2		ENSP00000463270	A2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70405 AN: 152000 Hom.: 18329 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.463 AC: 70399 AN: 152118 Hom.: 18324 Cov.: 33 AF XY: 0.464 AC XY: 34474 AN XY: 74370

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.435

Alfa AF: 0.537 Hom.: 11165

Bravo AF: 0.436

Asia WGS AF: 0.391 AC: 1362 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.020
DANN	Benign	0.37

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: rs999647; hg19: chr18-72571550;