18-74599610-A-G

Position:

• chr18-74599610-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.-54+1673A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,188 control chromosomes in the GnomAD database, including 56,082 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 0.86 (56082 hom., cov: 32)
• Consequence: ZNF407 NM_017757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

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 (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.-54+1673A>G		intron_variant		ENST00000299687.10	NP_060227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.-54+1673A>G		intron_variant		1	NM_017757.3	ENSP00000299687	P2
ZNF407	ENST00000582337.5	c.-54+1673A>G		intron_variant		5		ENSP00000462348

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130317 AN: 152070 Hom.: 56029 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.885

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

GnomAD4 genome AF: 0.857 AC: 130428 AN: 152188 Hom.: 56082 Cov.: 32 AF XY: 0.864 AC XY: 64275 AN XY: 74414

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.963

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.887

Alfa AF: 0.851 Hom.: 81025

Bravo AF: 0.860

Asia WGS AF: 0.970 AC: 3373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7245160; hg19: chr18-72266846;