chr4-288710-A-G

Variant names:

• chr4-288710-A-G
• rs11723261
• NM_001137608.3:c.226+6728T>C

Variant summary

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

The NM_001137608.3(ZNF732):​c.226+6728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,202 control chromosomes in the GnomAD database, including 1,906 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 0.14 (1906 hom., cov: 33)
• Consequence: ZNF732 NM_001137608.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 17 publications found

Genes affected

ZNF732 (HGNC:37138): (zinc finger protein 732) This gene encodes a kruppel-associated box-containing zinc finger protein (KRAB-ZFP). The encoded protein contains an N-terminal kruppel-associated box (KRAB) domain and sixteen C-terminal C2H2-type zinc finger domains. The KRAB-ZFPs represent the largest family of mammalian transcriptional repressors, which function through the recruitment of the nuclear co-factor KRAB-Associated Protein 1 (KAP1), to engage histone modifiers and induce heterochromatin formation. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137608.3. 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
	ZNF732	NM_001137608.3	MANE Select	c.226+6728T>C		intron	N/A	NP_001131080.1	B4DXR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF732	ENST00000419098.6	TSL:2 MANE Select	c.226+6728T>C		intron	N/A	ENSP00000415774.1	B4DXR9

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21477 AN: 152084 Hom.: 1899 Cov.: 33

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.141 AC: 21513 AN: 152202 Hom.: 1906 Cov.: 33 AF XY: 0.151 AC XY: 11245 AN XY: 74404

African (AFR) AF: 0.0508 AC: 2111 AN: 41554

American (AMR) AF: 0.246 AC: 3761 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3472

East Asian (EAS) AF: 0.161 AC: 831 AN: 5170

South Asian (SAS) AF: 0.213 AC: 1028 AN: 4826

European-Finnish (FIN) AF: 0.248 AC: 2629 AN: 10582

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10000 AN: 68010

Other (OTH) AF: 0.138 AC: 291 AN: 2110

Alfa AF: 0.141 Hom.: 4799

Bravo AF: 0.134

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.6
DANN	Benign	0.96
PhyloP100		0.16
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: rs11723261; hg19: chr4-282499;