7-100067194-A-G

Variant names:

• chr7-100067194-A-G
• rs7778571
• ENST00000413658.6:c.272-2282T>C

Variant summary

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

The ENST00000413658.6(ZNF3):​c.272-2282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,084 control chromosomes in the GnomAD database, including 3,492 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 0.21 (3492 hom., cov: 32)
• Consequence: ZNF3 ENST00000413658.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 12 publications found

Genes affected

ZNF3 (HGNC:13089): (zinc finger protein 3) Enables identical protein binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF3	NM_001371210.1	c.272-2282T>C		intron_variant	Intron 4 of 4		NP_001358139.1
ZNF3	NM_017715.4	c.272-2282T>C		intron_variant	Intron 5 of 5		NP_060185.2
ZNF3	NM_001318137.2	c.164-2282T>C		intron_variant	Intron 3 of 3		NP_001305066.1
ZNF3	XM_047420802.1	c.272-2282T>C		intron_variant	Intron 5 of 5		XP_047276758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF3	ENST00000413658.6	c.272-2282T>C		intron_variant	Intron 5 of 5	1		ENSP00000399951.2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31536 AN: 151966 Hom.: 3492 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.207 AC: 31545 AN: 152084 Hom.: 3492 Cov.: 32 AF XY: 0.204 AC XY: 15164 AN XY: 74356

African (AFR) AF: 0.192 AC: 7956 AN: 41500

American (AMR) AF: 0.169 AC: 2580 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5176

South Asian (SAS) AF: 0.166 AC: 798 AN: 4818

European-Finnish (FIN) AF: 0.213 AC: 2249 AN: 10572

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16465 AN: 67966

Other (OTH) AF: 0.207 AC: 436 AN: 2104

Alfa AF: 0.222 Hom.: 6798

Bravo AF: 0.201

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.21
PhyloP100		-0.30
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: rs7778571; hg19: chr7-99664817;