rs4803058

Positions:

• chr19-53191888-T-C

Variant summary

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

The NM_024733.5(ZNF665):​c.-46+1424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,072 control chromosomes in the GnomAD database, including 4,679 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 0.24 (4679 hom., cov: 32)
  • Exomes 𝑓: 0.22 (0 hom.)
• Consequence: ZNF665 NM_024733.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

Genes affected

ZNF665 (HGNC:25885): (zinc finger protein 665) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF665	NM_024733.5	c.-46+1424A>G		intron_variant		ENST00000396424.5	NP_079009.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF665	ENST00000396424.5	c.-46+1424A>G		intron_variant		2	NM_024733.5	ENSP00000379702	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36806 AN: 151938 Hom.: 4665 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.222 AC: 4 AN: 18 Hom.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.242 AC: 36863 AN: 152054 Hom.: 4679 Cov.: 32 AF XY: 0.242 AC XY: 17965 AN XY: 74328

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.204

Alfa AF: 0.241 Hom.: 3570

Bravo AF: 0.244

Asia WGS AF: 0.179 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.42

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: rs4803058; hg19: chr19-53695141;