chr19-36876230-A-G

Variant names:

• chr19-36876230-A-G
• rs826278
• NM_001242472.2:c.-46-555A>G

Variant summary

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

The NM_001242472.2(ZNF345):​c.-46-555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,110 control chromosomes in the GnomAD database, including 43,931 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 0.76 (43931 hom., cov: 31)
• Consequence: ZNF345 NM_001242472.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629
• Publications: 12 publications found

Genes affected

ZNF345 (HGNC:16367): (zinc finger protein 345) Enables sequence-specific double-stranded 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]

ENSG00000291239 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242472.2. 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
	ZNF345	NM_001242472.2	MANE Select	c.-46-555A>G		intron	N/A	NP_001229401.1
	ZNF345	NM_001242474.2		c.-46-555A>G		intron	N/A	NP_001229403.1
	ZNF345	NM_001242475.2		c.-46-555A>G		intron	N/A	NP_001229404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF345	ENST00000420450.6	TSL:1 MANE Select	c.-46-555A>G		intron	N/A	ENSP00000431216.1
	ENSG00000291239	ENST00000706165.1		c.-423-16588A>G		intron	N/A	ENSP00000516244.1
	ZNF345	ENST00000589046.1	TSL:1	c.-46-555A>G		intron	N/A	ENSP00000465431.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114930 AN: 151992 Hom.: 43891 Cov.: 31

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.756 AC: 115034 AN: 152110 Hom.: 43931 Cov.: 31 AF XY: 0.759 AC XY: 56408 AN XY: 74352

African (AFR) AF: 0.834 AC: 34636 AN: 41516

American (AMR) AF: 0.777 AC: 11868 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2523 AN: 3468

East Asian (EAS) AF: 0.922 AC: 4770 AN: 5172

South Asian (SAS) AF: 0.841 AC: 4053 AN: 4822

European-Finnish (FIN) AF: 0.696 AC: 7356 AN: 10566

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47369 AN: 67984

Other (OTH) AF: 0.760 AC: 1602 AN: 2108

Alfa AF: 0.719 Hom.: 169394

Bravo AF: 0.766

Asia WGS AF: 0.857 AC: 2980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.84
PhyloP100		0.63
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: rs826278; hg19: chr19-37367132;