rs10853854

Positions:

• chr19-52728875-G-A

Variant summary

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

The NM_001161499.2(ZNF611):​c.-121-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 166,670 control chromosomes in the GnomAD database, including 11,073 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 0.37 (10543 hom., cov: 32)
  • Exomes 𝑓: 0.27 (530 hom.)
• Consequence: ZNF611 NM_001161499.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF611	NM_001161499.2	c.-121-44C>T		intron_variant		ENST00000652185.1	NP_001154971.1
ZNF611	NM_001161500.2	c.-121-44C>T		intron_variant			NP_001154972.1
ZNF611	NM_001161501.1	c.-201-44C>T		intron_variant			NP_001154973.1
ZNF611	NM_030972.3	c.-244-44C>T		intron_variant			NP_112234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF611	ENST00000652185.1	c.-121-44C>T		intron_variant			NM_001161499.2	ENSP00000498713	P1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55506 AN: 151846 Hom.: 10529 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.269 AC: 3955 AN: 14706 Hom.: 530 Cov.: 0 AF XY: 0.267 AC XY: 2389 AN XY: 8962

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.366 AC: 55566 AN: 151964 Hom.: 10543 Cov.: 32 AF XY: 0.366 AC XY: 27202 AN XY: 74286

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.350

Alfa AF: 0.345 Hom.: 1563

Bravo AF: 0.372

Asia WGS AF: 0.366 AC: 1271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.2
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10853854; hg19: chr19-53232128; COSMIC: COSV60540593; COSMIC: COSV60540593;