chr19-52957608-G-A

Variant names:

• chr19-52957608-G-A
• rs11084211
• NM_001202457.3:c.-15-1504C>T

Variant summary

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

The NM_001202457.3(ZNF816):​c.-15-1504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,958 control chromosomes in the GnomAD database, including 15,040 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 0.43 (15040 hom., cov: 31)
• Consequence: ZNF816 NM_001202457.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 9 publications found

Genes affected

ZNF816 (HGNC:26995): (zinc finger protein 816) 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 integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF816-ZNF321P (HGNC:38879): (ZNF816-ZNF321P readthrough) This locus represents naturally occurring read-through transcription between the zinc finger protein 816 (ZNF816) gene and the zinc finger protein 321 (ZNF321) pseudogene on chromosome 19. The read-through transcript encodes a KRAB domain-containing protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus encoded by exon structure from the downstream pseudogene. [provided by RefSeq, Jan 2011]

ENSG00000269082 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202457.3. 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
	ZNF816	NM_001202457.3	MANE Select	c.-15-1504C>T		intron	N/A	NP_001189386.1
	ZNF816	NM_001031665.4		c.-15-1504C>T		intron	N/A	NP_001026835.1
	ZNF816	NM_001202456.3		c.-15-1504C>T		intron	N/A	NP_001189385.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF816	ENST00000444460.7	TSL:1 MANE Select	c.-15-1504C>T		intron	N/A	ENSP00000403266.2
	ZNF816	ENST00000357666.8	TSL:1	c.-15-1504C>T		intron	N/A	ENSP00000350295.4
	ZNF816-ZNF321P	ENST00000391777.3	TSL:2	c.-15-1504C>T		intron	N/A	ENSP00000375656.3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64710 AN: 151840 Hom.: 15016 Cov.: 31

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.426 AC: 64777 AN: 151958 Hom.: 15040 Cov.: 31 AF XY: 0.425 AC XY: 31543 AN XY: 74260

African (AFR) AF: 0.619 AC: 25630 AN: 41424

American (AMR) AF: 0.348 AC: 5314 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1532 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1960 AN: 5154

South Asian (SAS) AF: 0.435 AC: 2094 AN: 4814

European-Finnish (FIN) AF: 0.304 AC: 3211 AN: 10554

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23561 AN: 67948

Other (OTH) AF: 0.437 AC: 924 AN: 2114

Alfa AF: 0.369 Hom.: 7274

Bravo AF: 0.436

Asia WGS AF: 0.411 AC: 1431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.71
PhyloP100		-1.0
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: rs11084211; hg19: chr19-53460861;