chr12-133048690-A-T

Variant names:

• chr12-133048690-A-T
• rs7314140
• NM_001289971.2:c.143-63A>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001289971.2(ZNF84):​c.143-63A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,296,676 control chromosomes in the GnomAD database, including 123,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16879 hom., cov: 32)
  • Exomes 𝑓: 0.43 (106166 hom.)
• Consequence: ZNF84 NM_001289971.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.858

Genes affected

ZNF84 (HGNC:13159): (zinc finger protein 84) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-133048690-A-T is Benign according to our data. Variant chr12-133048690-A-T is described in ClinVar as [Benign]. Clinvar id is 982074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF84	NM_001289971.2	c.143-63A>T		intron_variant	Intron 3 of 4	ENST00000539354.6	NP_001276900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF84	ENST00000539354.6	c.143-63A>T		intron_variant	Intron 3 of 4	1	NM_001289971.2	ENSP00000445549.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69907 AN: 151844 Hom.: 16869 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.426 AC: 487268 AN: 1144716 Hom.: 106166 Cov.: 14 AF XY: 0.427 AC XY: 247702 AN XY: 580166

Gnomad4 AFR exome AF: 0.603

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.460 AC: 69944 AN: 151960 Hom.: 16879 Cov.: 32 AF XY: 0.455 AC XY: 33823 AN XY: 74258

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.401

Alfa AF: 0.249 Hom.: 423

Bravo AF: 0.454

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

Pathology and Clinical Laboratory Medicine, King Fahad Medical City

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs7314140; hg19: chr12-133625276; COSMIC: COSV59654452; COSMIC: COSV59654452;