chr3-75740820-G-A

Variant names:

• chr3-75740820-G-A
• rs1963442
• NM_001290208.3:c.277+456C>T

Variant summary

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

The NM_001290208.3(ZNF717):​c.277+456C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 140,264 control chromosomes in the GnomAD database, including 36,594 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 0.75 (36594 hom., cov: 31)
• Consequence: ZNF717 NM_001290208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• Publications: 2 publications found

Genes affected

ZNF717 (HGNC:29448): (zinc finger protein 717) This gene encodes a Kruppel-associated box (KRAB) zinc-finger protein, which belongs to a large group of transcriptional regulators in mammals. These proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation and apoptosis, and in regulating viral replication and transcription. A pseudogene of this gene was identified on chromosome 1. [provided by RefSeq, May 2016]

LINC00960 (HGNC:48710): (long intergenic non-protein coding RNA 960)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290208.3. 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
	ZNF717	NM_001290208.3	MANE Select	c.277+456C>T		intron	N/A	NP_001277137.1
	ZNF717	NM_001128223.3		c.277+456C>T		intron	N/A	NP_001121695.1
	ZNF717	NM_001290209.3		c.127+456C>T		intron	N/A	NP_001277138.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF717	ENST00000652011.2	MANE Select	c.277+456C>T		intron	N/A	ENSP00000498738.1
	LINC00960	ENST00000668145.2		n.744G>A		non_coding_transcript_exon	Exon 2 of 2
	ZNF717	ENST00000850935.1		c.379+456C>T		intron	N/A	ENSP00000521016.1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 104523 AN: 140164 Hom.: 36557 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.746 AC: 104605 AN: 140264 Hom.: 36594 Cov.: 31 AF XY: 0.748 AC XY: 51319 AN XY: 68576

African (AFR) AF: 0.762 AC: 29686 AN: 38952

American (AMR) AF: 0.758 AC: 10613 AN: 14006

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2325 AN: 3154

East Asian (EAS) AF: 0.827 AC: 3954 AN: 4780

South Asian (SAS) AF: 0.810 AC: 3673 AN: 4534

European-Finnish (FIN) AF: 0.722 AC: 7164 AN: 9920

Middle Eastern (MID) AF: 0.768 AC: 212 AN: 276

European-Non Finnish (NFE) AF: 0.725 AC: 44903 AN: 61900

Other (OTH) AF: 0.760 AC: 1469 AN: 1932

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism

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: rs1963442; hg19: chr3-75789971;