1-247003441-C-G

Variant names:

• chr1-247003441-C-G
• rs2642956
• NM_020394.5:c.4-3367G>C

Variant summary

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

The NM_020394.5(ZNF695):​c.4-3367G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,972 control chromosomes in the GnomAD database, including 32,190 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 0.64 (32190 hom., cov: 32)
• Consequence: ZNF695 NM_020394.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020394.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF695	NM_020394.5	MANE Select	c.4-3367G>C		intron	N/A	NP_065127.5
	ZNF695	NM_001204221.2		c.4-3367G>C		intron	N/A	NP_001191150.2
	ZNF695	NR_037892.2		n.153-3367G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF695	ENST00000339986.8	TSL:1 MANE Select	c.4-3367G>C		intron	N/A	ENSP00000341236.7
	ZNF695	ENST00000487338.6	TSL:1	c.4-3367G>C		intron	N/A	ENSP00000429736.1
	ZNF695	ENST00000366504.6	TSL:1	n.4-3367G>C		intron	N/A	ENSP00000355460.2

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96779 AN: 151854 Hom.: 32168 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.637 AC: 96827 AN: 151972 Hom.: 32190 Cov.: 32 AF XY: 0.645 AC XY: 47888 AN XY: 74262

African (AFR) AF: 0.448 AC: 18537 AN: 41412

American (AMR) AF: 0.741 AC: 11316 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2448 AN: 3472

East Asian (EAS) AF: 0.993 AC: 5150 AN: 5184

South Asian (SAS) AF: 0.716 AC: 3450 AN: 4820

European-Finnish (FIN) AF: 0.726 AC: 7647 AN: 10534

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46112 AN: 67964

Other (OTH) AF: 0.650 AC: 1372 AN: 2110

Alfa AF: 0.531 Hom.: 1533

Bravo AF: 0.633

Asia WGS AF: 0.847 AC: 2943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		0.21
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: rs2642956; hg19: chr1-247166743;