5-124721248-G-A

Variant names:

• chr5-124721248-G-A
• rs7727239
• NM_020747.3:c.907-19979C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020747.3. 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
	ZNF608	NM_020747.3	MANE Select	c.907-19979C>T		intron	N/A	NP_065798.2
	ZNF608	NM_001385619.1		c.907-19979C>T		intron	N/A	NP_001372548.1
	ZNF608	NM_001385620.1		c.907-19979C>T		intron	N/A	NP_001372549.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF608	ENST00000513986.2	TSL:2 MANE Select	c.907-19979C>T		intron	N/A	ENSP00000421899.2
	ZNF608	ENST00000306315.9	TSL:1	c.907-19979C>T		intron	N/A	ENSP00000307746.5
	ZNF608	ENST00000504926.5	TSL:1	c.-375-19979C>T		intron	N/A	ENSP00000427657.1

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

African (AFR) AF: 0.0937 AC: 3889 AN: 41512

American (AMR) AF: 0.268 AC: 4099 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3470

East Asian (EAS) AF: 0.127 AC: 655 AN: 5174

South Asian (SAS) AF: 0.240 AC: 1154 AN: 4814

European-Finnish (FIN) AF: 0.189 AC: 1992 AN: 10566

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13482 AN: 67992

Other (OTH) AF: 0.190 AC: 400 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-0.098
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: rs7727239; hg19: chr5-124056941;