rs4802987

Positions:

• chr19-52730020-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161499.2(ZNF611):​c.-221-15A>G variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF611	NM_001161499.2	c.-221-15A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000652185.1	NP_001154971.1
ZNF611	NM_001161500.2	c.-121-1189A>G		intron_variant			NP_001154972.1
ZNF611	NM_001161501.1	c.-301-15A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_001154973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF611	ENST00000652185.1	c.-221-15A>G		splice_polypyrimidine_tract_variant, intron_variant			NM_001161499.2	ENSP00000498713	P1

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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.258

Alfa AF: 0.275 Hom.: 12158

Bravo AF: 0.279

Asia WGS AF: 0.179 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.8
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs4802987; hg19: chr19-53233273;