rs8109854

Variant names:

• chr19-52004866-C-T
• rs8109854
• NM_001199324.2:c.-189-966G>A

Variant summary

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

The NM_001199324.2(ZNF615):​c.-189-966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,904 control chromosomes in the GnomAD database, including 15,233 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 0.42 (15233 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: ZNF615 NM_001199324.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 2 publications found

Genes affected

ZNF615 (HGNC:24740): (zinc finger protein 615) Predicted to enable DNA-binding transcription activator 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 by RNA polymerase II. Predicted to be active 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF615	NM_001199324.2	c.-189-966G>A		intron_variant	Intron 2 of 6	ENST00000598071.6	NP_001186253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF615	ENST00000598071.6	c.-189-966G>A		intron_variant	Intron 2 of 6	1	NM_001199324.2	ENSP00000471041.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63264 AN: 151780 Hom.: 15179 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.417 AC: 63390 AN: 151900 Hom.: 15233 Cov.: 32 AF XY: 0.424 AC XY: 31450 AN XY: 74234

African (AFR) AF: 0.650 AC: 26920 AN: 41416

American (AMR) AF: 0.441 AC: 6734 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3464

East Asian (EAS) AF: 0.508 AC: 2624 AN: 5170

South Asian (SAS) AF: 0.566 AC: 2729 AN: 4822

European-Finnish (FIN) AF: 0.306 AC: 3208 AN: 10492

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18790 AN: 67946

Other (OTH) AF: 0.413 AC: 872 AN: 2112

Alfa AF: 0.366 Hom.: 1551

Bravo AF: 0.436

Asia WGS AF: 0.588 AC: 2042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.56
PhyloP100		-0.44
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: rs8109854; hg19: chr19-52508119;