ENST00000487338.6:c.488+2477T>C

Variant names:

• chr1-246965218-A-G
• rs1779984
• ENST00000487338.6:c.488+2477T>C

Variant summary

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

The ENST00000487338.6(ZNF695):​c.488+2477T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,800 control chromosomes in the GnomAD database, including 32,600 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 0.63 (32600 hom., cov: 30)
• Consequence: ZNF695 ENST00000487338.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 1 publications found

Genes affected

ZNF695 (HGNC:30954): (zinc finger protein 695) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF670-ZNF695 (HGNC:49200): (ZNF670-ZNF695 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 670 (ZNF670) and zinc finger protein 695 (ZNF695) genes on chromosome 1. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487338.6. 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
	ZNF695	NM_001204221.2		c.488+2477T>C		intron	N/A	NP_001191150.2
	ZNF695	NR_037892.2		n.641+2477T>C		intron	N/A
	ZNF670-ZNF695	NR_037894.2		n.836+2477T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF695	ENST00000487338.6	TSL:1	c.488+2477T>C		intron	N/A	ENSP00000429736.1
	ZNF695	ENST00000366504.6	TSL:1	n.*90+2477T>C		intron	N/A	ENSP00000355460.2
	ZNF670-ZNF695	ENST00000465049.6	TSL:5	n.*207+2477T>C		intron	N/A	ENSP00000428213.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95673 AN: 151682 Hom.: 32540 Cov.: 30

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.631 AC: 95786 AN: 151800 Hom.: 32600 Cov.: 30 AF XY: 0.635 AC XY: 47081 AN XY: 74182

African (AFR) AF: 0.903 AC: 37450 AN: 41472

American (AMR) AF: 0.632 AC: 9641 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1567 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2629 AN: 5120

South Asian (SAS) AF: 0.537 AC: 2581 AN: 4806

European-Finnish (FIN) AF: 0.584 AC: 6145 AN: 10524

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33711 AN: 67866

Other (OTH) AF: 0.629 AC: 1320 AN: 2098

Alfa AF: 0.563 Hom.: 3055

Bravo AF: 0.648

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.060
DANN	Benign	0.074
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1779984; hg19: chr1-247128520;