rs12935091

Positions:

• chr16-71491305-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000564225.5(ZNF19):​c.-190+3649T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 152,294 control chromosomes in the GnomAD database, including 91 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 0.030 (91 hom., cov: 32)
• Consequence: ZNF19 ENST00000564225.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

Genes affected

ZNF19 (HGNC:12981): (zinc finger protein 19) The protein encoded by this gene contains a zinc finger, a nucleic acid-binding domain present in many transcription factors. This gene is located in a region next to ZNF23, a gene also encoding a zinc finger protein, on chromosome 16. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0297 (4529/152294) while in subpopulation NFE AF= 0.0474 (3223/68016). AF 95% confidence interval is 0.046. There are 91 homozygotes in gnomad4. There are 2104 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 91 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF19	ENST00000564225.5	c.-190+3649T>C		intron_variant		2		ENSP00000455575
ZNF19	ENST00000566202.5	c.-189-6557T>C		intron_variant		5		ENSP00000454862
ZNF19	ENST00000568446.1	n.324+3649T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4530 AN: 152176 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.00849

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0267

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

GnomAD4 genome AF: 0.0297 AC: 4529 AN: 152294 Hom.: 91 Cov.: 32 AF XY: 0.0283 AC XY: 2104 AN XY: 74458

Gnomad4 AFR AF: 0.00847

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.0474

Gnomad4 OTH AF: 0.0269

Alfa AF: 0.0386 Hom.: 56

Bravo AF: 0.0268

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12935091; hg19: chr16-71525208;