18-74599610-A-G

Variant names:

• chr18-74599610-A-G
• rs7245160
• NM_017757.3:c.-54+1673A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ZNF407 Gene-Disease associations (from GenCC):

• short stature, impaired intellectual development, microcephaly, hypotonia, and ocular anomalies

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017757.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF407	NM_017757.3	MANE Select	c.-54+1673A>G		intron	N/A	NP_060227.2	Q9C0G0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF407	ENST00000299687.10	TSL:1 MANE Select	c.-54+1673A>G		intron	N/A	ENSP00000299687.4	Q9C0G0-1
	ZNF407	ENST00000949102.1		c.-54+1673A>G		intron	N/A	ENSP00000619161.1
	ZNF407	ENST00000582337.5	TSL:5	c.-54+1673A>G		intron	N/A	ENSP00000462348.1	Q9C0G0-3

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

African (AFR) AF: 0.833 AC: 34538 AN: 41472

American (AMR) AF: 0.920 AC: 14078 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3088 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5185 AN: 5188

South Asian (SAS) AF: 0.963 AC: 4657 AN: 4834

European-Finnish (FIN) AF: 0.885 AC: 9385 AN: 10602

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56547 AN: 68006

Other (OTH) AF: 0.887 AC: 1873 AN: 2112

Alfa AF: 0.848 Hom.: 124345

Bravo AF: 0.860

Asia WGS AF: 0.970 AC: 3373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7245160; hg19: chr18-72266846;