rs12974834

Positions:

• chr19-52660901-T-C

Variant summary

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

The NM_001396016.1(LOC122539214):​c.-19-58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 153,620 control chromosomes in the GnomAD database, including 977 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 0.11 (969 hom., cov: 30)
  • Exomes 𝑓: 0.094 (8 hom.)
• Consequence: LOC122539214 NM_001396016.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

Genes affected

LOC122539214 (HGNC:):

ZNF83 (HGNC:13158): (zinc finger protein 83) 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 located 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC122539214	NM_001396016.1	c.-19-58A>G		intron_variant		ENST00000598322.3	NP_001382945.1
ZNF83	NM_001277948.2	c.-530-58A>G		intron_variant			NP_001264877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000598322.3	c.-19-58A>G		intron_variant			NM_001396016.1	ENSP00000506273	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16205 AN: 151956 Hom.: 966 Cov.: 30

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0900

GnomAD4 exome AF: 0.0944 AC: 146 AN: 1546 Hom.: 8 AF XY: 0.100 AC XY: 87 AN XY: 866

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0577

Gnomad4 FIN exome AF: 0.0985

Gnomad4 NFE exome AF: 0.0793

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.107 AC: 16222 AN: 152074 Hom.: 969 Cov.: 30 AF XY: 0.104 AC XY: 7724 AN XY: 74342

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.0807

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0520

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0890

Alfa AF: 0.105 Hom.: 123

Bravo AF: 0.108

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12974834; hg19: chr19-53164154;