18-74859594-A-G

Variant names:

• chr18-74859594-A-G
• rs999647
• NM_017757.3:c.4878-17603A>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.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
• Publications: 4 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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 (NFE) allele frequency at 95% confidence interval = 0.575 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF407	NM_017757.3	MANE Select	c.4878-17603A>G		intron	N/A	NP_060227.2
	ZNF407	NM_001384475.1		c.4878-17603A>G		intron	N/A	NP_001371404.1
	ZNF407	NM_001146189.1		c.4878-17603A>G		intron	N/A	NP_001139661.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF407	ENST00000299687.10	TSL:1 MANE Select	c.4878-17603A>G		intron	N/A	ENSP00000299687.4
	ZNF407	ENST00000577538.5	TSL:2	c.4878-17603A>G		intron	N/A	ENSP00000463270.1

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

African (AFR) AF: 0.234 AC: 9732 AN: 41508

American (AMR) AF: 0.438 AC: 6690 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1715 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2091 AN: 5176

South Asian (SAS) AF: 0.420 AC: 2027 AN: 4828

European-Finnish (FIN) AF: 0.689 AC: 7297 AN: 10586

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.580 AC: 39396 AN: 67960

Other (OTH) AF: 0.435 AC: 918 AN: 2110

Alfa AF: 0.529 Hom.: 41408

Bravo AF: 0.436

Asia WGS AF: 0.391 AC: 1362 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.020
DANN	Benign	0.37
PhyloP100		-2.1
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: rs999647; hg19: chr18-72571550;