rs4803055

Positions:

• chr19-53168784-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.143-2437A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,018 control chromosomes in the GnomAD database, including 23,148 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 0.51 (23148 hom., cov: 32)
• Consequence: ZNF665 NM_024733.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF665	NM_024733.5	c.143-2437A>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.143-2437A>G		intron_variant		2	NM_024733.5	ENSP00000379702.2
ZNF665	ENST00000650736.1	c.143-2437A>G		intron_variant				ENSP00000498600.1
ZNF665	ENST00000600412.1	c.-53-2437A>G		intron_variant		5		ENSP00000469154.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77026 AN: 151900 Hom.: 23138 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.507 AC: 77055 AN: 152018 Hom.: 23148 Cov.: 32 AF XY: 0.515 AC XY: 38285 AN XY: 74284

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.518

Alfa AF: 0.576 Hom.: 4750

Bravo AF: 0.486

Asia WGS AF: 0.645 AC: 2236 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.44

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: rs4803055; hg19: chr19-53672037;