7-149201983-A-T

Variant names:

• chr7-149201983-A-T
• rs1211759
• NM_003575.4:c.585+3231A>T

Variant summary

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

The ENST00000610704.5(ZNF282):​c.585+3231A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 151,760 control chromosomes in the GnomAD database, including 54,022 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 0.84 (54022 hom., cov: 27)
• Consequence: ZNF282 ENST00000610704.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 2 publications found

Genes affected

ZNF282 (HGNC:13076): (zinc finger protein 282) Enables sequence-specific double-stranded DNA 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000610704.5. 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
	ZNF282	NM_003575.4	MANE Select	c.585+3231A>T		intron	N/A	NP_003566.1
	ZNF282	NM_001303481.3		c.585+3231A>T		intron	N/A	NP_001290410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF282	ENST00000610704.5	TSL:1 MANE Select	c.585+3231A>T		intron	N/A	ENSP00000477841.1
	ZNF282	ENST00000850624.1		c.585+3231A>T		intron	N/A	ENSP00000520909.1
	ZNF282	ENST00000479907.1	TSL:2	c.585+3231A>T		intron	N/A	ENSP00000418840.1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127375 AN: 151642 Hom.: 53997 Cov.: 27

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.840 AC: 127452 AN: 151760 Hom.: 54022 Cov.: 27 AF XY: 0.844 AC XY: 62569 AN XY: 74150

African (AFR) AF: 0.700 AC: 28897 AN: 41288

American (AMR) AF: 0.872 AC: 13297 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3268 AN: 3468

East Asian (EAS) AF: 0.965 AC: 4968 AN: 5146

South Asian (SAS) AF: 0.905 AC: 4345 AN: 4800

European-Finnish (FIN) AF: 0.887 AC: 9348 AN: 10538

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60528 AN: 67958

Other (OTH) AF: 0.860 AC: 1815 AN: 2110

Alfa AF: 0.865 Hom.: 6716

Bravo AF: 0.833

Asia WGS AF: 0.887 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.48
DANN	Benign	0.46
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1211759; hg19: chr7-148899075;