19-52730020-T-C

Variant names:

• chr19-52730020-T-C
• rs4802987
• NM_001161499.2:c.-221-15A>G

Variant summary

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

The NM_001161499.2(ZNF611):​c.-221-15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,004 control chromosomes in the GnomAD database, including 5,910 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 0.28 (5910 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF611 NM_001161499.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 9 publications found

Genes affected

ZNF611 (HGNC:28766): (zinc finger protein 611) 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 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161499.2. 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
	ZNF611	NM_001161499.2	MANE Select	c.-221-15A>G		intron	N/A	NP_001154971.1
	ZNF611	NM_001161500.2		c.-121-1189A>G		intron	N/A	NP_001154972.1
	ZNF611	NM_001161501.1		c.-301-15A>G		intron	N/A	NP_001154973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF611	ENST00000652185.1	MANE Select	c.-221-15A>G		intron	N/A	ENSP00000498713.1
	ZNF611	ENST00000595001.5	TSL:1	n.-344-15A>G		intron	N/A	ENSP00000471243.1
	ZNF611	ENST00000540744.5	TSL:4	c.-121-1189A>G		intron	N/A	ENSP00000439211.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42010 AN: 151886 Hom.: 5901 Cov.: 30

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.261

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.277 AC: 42031 AN: 152004 Hom.: 5910 Cov.: 30 AF XY: 0.271 AC XY: 20169 AN XY: 74288

African (AFR) AF: 0.315 AC: 13033 AN: 41440

American (AMR) AF: 0.244 AC: 3720 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3466

East Asian (EAS) AF: 0.106 AC: 550 AN: 5172

South Asian (SAS) AF: 0.244 AC: 1175 AN: 4824

European-Finnish (FIN) AF: 0.250 AC: 2645 AN: 10560

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19322 AN: 67978

Other (OTH) AF: 0.258 AC: 542 AN: 2102

Alfa AF: 0.277 Hom.: 26221

Bravo AF: 0.279

Asia WGS AF: 0.179 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.8
DANN	Benign	0.49
PhyloP100		-0.29
PromoterAI		0.0076	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs4802987; hg19: chr19-53233273;