rs258575

Variant names:

• chr19-20001455-T-C
• rs258575

Variant summary

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

The variant allele was found at a frequency of 0.174 in 152,186 control chromosomes in the GnomAD database, including 2,547 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 0.17 (2547 hom., cov: 32)
• Consequence: BNIP3P12 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 4 publications found

Genes affected

BNIP3P12 (HGNC:49692):

ZNF682 (HGNC:28857): (zinc finger protein 682) 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNIP3P12		n.20001455T>C		intragenic_variant
ZNF682	XR_007067033.1	n.3345+3181A>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF682	ENST00000596019.5	c.227-4192A>G		intron_variant	Intron 3 of 3	5		ENSP00000472444.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26486 AN: 152068 Hom.: 2541 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.174 AC: 26506 AN: 152186 Hom.: 2547 Cov.: 32 AF XY: 0.173 AC XY: 12903 AN XY: 74402

African (AFR) AF: 0.138 AC: 5724 AN: 41528

American (AMR) AF: 0.170 AC: 2595 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2232 AN: 5158

South Asian (SAS) AF: 0.121 AC: 583 AN: 4824

European-Finnish (FIN) AF: 0.180 AC: 1903 AN: 10596

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12358 AN: 68002

Other (OTH) AF: 0.171 AC: 361 AN: 2114

Alfa AF: 0.174 Hom.: 315

Bravo AF: 0.174

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.42
PhyloP100		-2.4
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: rs258575; hg19: chr19-20112264;