chr7-149216553-G-T

Variant names:

• chr7-149216553-G-T
• rs1202389
• NM_003575.4:c.1180+2739G>T

Variant summary

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

The NM_003575.4(ZNF282):​c.1180+2739G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 152,280 control chromosomes in the GnomAD database, including 405 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 0.071 (405 hom., cov: 32)
• Consequence: ZNF282 NM_003575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF282	NM_003575.4	c.1180+2739G>T		intron_variant	Intron 7 of 7	ENST00000610704.5	NP_003566.1
ZNF282	NM_001303481.3	c.1180+2739G>T		intron_variant	Intron 7 of 8		NP_001290410.1
ZNF282	XM_006716151.5	c.1183+2739G>T		intron_variant	Intron 7 of 7		XP_006716214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF282	ENST00000610704.5	c.1180+2739G>T		intron_variant	Intron 7 of 7	1	NM_003575.4	ENSP00000477841.1
ZNF282	ENST00000850624.1	c.1180+2739G>T		intron_variant	Intron 7 of 7			ENSP00000520909.1
ZNF282	ENST00000479907.1	c.1180+2739G>T		intron_variant	Intron 7 of 8	2		ENSP00000418840.1
ZNF282	ENST00000470381.1	n.278+2739G>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10838 AN: 152162 Hom.: 403 Cov.: 32

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0712 AC: 10848 AN: 152280 Hom.: 405 Cov.: 32 AF XY: 0.0699 AC XY: 5205 AN XY: 74480

African (AFR) AF: 0.0925 AC: 3842 AN: 41550

American (AMR) AF: 0.0614 AC: 939 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0441 AC: 213 AN: 4830

European-Finnish (FIN) AF: 0.0378 AC: 401 AN: 10612

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0705 AC: 4797 AN: 68020

Other (OTH) AF: 0.0820 AC: 173 AN: 2110

Alfa AF: 0.0760 Hom.: 762

Bravo AF: 0.0748

Asia WGS AF: 0.0250 AC: 86 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	3.8
DANN	Benign	0.67
PhyloP100		0.40
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: rs1202389; hg19: chr7-148913645;