rs7727239

Positions:

• chr5-124721248-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020747.3(ZNF608):​c.907-19979C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,122 control chromosomes in the GnomAD database, including 2,630 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 0.17 (2630 hom., cov: 30)
• Consequence: ZNF608 NM_020747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

Genes affected

ZNF608 (HGNC:29238): (zinc finger protein 608) Predicted to enable metal ion binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF608	NM_020747.3	c.907-19979C>T		intron_variant		ENST00000513986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF608	ENST00000513986.2	c.907-19979C>T		intron_variant		2	NM_020747.3	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26439 AN: 152004 Hom.: 2624 Cov.: 30

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.174 AC: 26454 AN: 152122 Hom.: 2630 Cov.: 30 AF XY: 0.176 AC XY: 13057 AN XY: 74368

Gnomad4 AFR AF: 0.0937

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.190

Alfa AF: 0.200 Hom.: 566

Bravo AF: 0.177

Asia WGS AF: 0.173 AC: 602 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	2.0
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7727239; hg19: chr5-124056941;