18-74643830-G-C

Variant names:

• chr18-74643830-G-C
• rs4243289
• NM_017757.3:c.4802+2708G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017757.3(ZNF407):​c.4802+2708G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,730 control chromosomes in the GnomAD database, including 19,107 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 0.48 (19107 hom., cov: 32)
• Consequence: ZNF407 NM_017757.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• 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: 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF407	NM_017757.3	c.4802+2708G>C		intron_variant	Intron 3 of 8	ENST00000299687.10	NP_060227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF407	ENST00000299687.10	c.4802+2708G>C		intron_variant	Intron 3 of 8	1	NM_017757.3	ENSP00000299687.4
ZNF407	ENST00000577538.5	c.4802+2708G>C		intron_variant	Intron 2 of 6	2		ENSP00000463270.1
ZNF407	ENST00000309902.10	c.4802+2708G>C		intron_variant	Intron 2 of 3	2		ENSP00000310359.5
ZNF407	ENST00000582337.5	c.4802+2708G>C		intron_variant	Intron 3 of 4	5		ENSP00000462348.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72990 AN: 151612 Hom.: 19064 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.482 AC: 73089 AN: 151730 Hom.: 19107 Cov.: 32 AF XY: 0.471 AC XY: 34912 AN XY: 74148

African (AFR) AF: 0.687 AC: 28471 AN: 41462

American (AMR) AF: 0.342 AC: 5220 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1593 AN: 3464

East Asian (EAS) AF: 0.184 AC: 952 AN: 5172

South Asian (SAS) AF: 0.360 AC: 1734 AN: 4814

European-Finnish (FIN) AF: 0.370 AC: 3904 AN: 10542

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29779 AN: 67730

Other (OTH) AF: 0.449 AC: 942 AN: 2096

Alfa AF: 0.291 Hom.: 649

Bravo AF: 0.487

Asia WGS AF: 0.303 AC: 1051 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.31
PhyloP100		-0.44
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: rs4243289; hg19: chr18-72355786;