rs12974834

Variant names:

• chr19-52660901-T-C
• rs12974834
• NM_001396016.1:c.-19-58A>G

Variant summary

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

The ENST00000598322.3(ENSG00000269825):​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: ENSG00000269825 ENST00000598322.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734
• Publications: 5 publications found

Genes affected

LOC122539214 (HGNC:0):

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]

ENSG00000269825 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000598322.3. 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
	LOC122539214	NM_001396016.1	MANE Select	c.-19-58A>G		intron	N/A	NP_001382945.1
	ZNF83	NM_001277945.2		c.-657-58A>G		intron	N/A	NP_001264874.1
	ZNF83	NM_001277946.2		c.-442-58A>G		intron	N/A	NP_001264875.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000269825	ENST00000598322.3	TSL:6 MANE Select	c.-19-58A>G		intron	N/A	ENSP00000506273.1
	ENSG00000269825	ENST00000687234.1		c.-67-58A>G		intron	N/A	ENSP00000509087.2
	ENSG00000269825	ENST00000594682.6	TSL:4	n.-67-58A>G		intron	N/A	ENSP00000472147.2

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

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.167 AC: 2 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 3 AN: 8

East Asian (EAS) AF: 0.00 AC: 0 AN: 36

South Asian (SAS) AF: 0.0577 AC: 3 AN: 52

European-Finnish (FIN) AF: 0.0985 AC: 106 AN: 1076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0793 AC: 26 AN: 328

Other (OTH) AF: 0.208 AC: 5 AN: 24

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

African (AFR) AF: 0.147 AC: 6101 AN: 41466

American (AMR) AF: 0.0744 AC: 1135 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0520 AC: 250 AN: 4810

European-Finnish (FIN) AF: 0.0976 AC: 1033 AN: 10580

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7143 AN: 67998

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.106 Hom.: 134

Bravo AF: 0.108

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.95
PhyloP100		-0.73
PromoterAI		0.036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12974834; hg19: chr19-53164154;