12-133048690-A-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF84	NM_001289971.2	MANE Select	c.143-63A>T		intron	N/A	NP_001276900.1	P51523
	ZNF84	NM_001127372.3		c.143-63A>T		intron	N/A	NP_001120844.1	P51523
	ZNF84	NM_001289972.2		c.143-63A>T		intron	N/A	NP_001276901.1	P51523

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF84	ENST00000539354.6	TSL:1 MANE Select	c.143-63A>T		intron	N/A	ENSP00000445549.1	P51523
	ZNF84	ENST00000327668.11	TSL:1	c.143-63A>T		intron	N/A	ENSP00000331465.7	P51523
	ZNF84	ENST00000392319.6	TSL:1	c.143-63A>T		intron	N/A	ENSP00000376133.2	P51523

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

African (AFR) AF: 0.603 AC: 16138 AN: 26742

American (AMR) AF: 0.306 AC: 11805 AN: 38564

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 8459 AN: 23010

East Asian (EAS) AF: 0.223 AC: 8213 AN: 36818

South Asian (SAS) AF: 0.458 AC: 34844 AN: 76086

European-Finnish (FIN) AF: 0.425 AC: 21283 AN: 50024

Middle Eastern (MID) AF: 0.368 AC: 1886 AN: 5128

European-Non Finnish (NFE) AF: 0.434 AC: 364069 AN: 839260

Other (OTH) AF: 0.419 AC: 20571 AN: 49084

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

African (AFR) AF: 0.600 AC: 24849 AN: 41420

American (AMR) AF: 0.351 AC: 5361 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1151 AN: 5164

South Asian (SAS) AF: 0.452 AC: 2172 AN: 4806

European-Finnish (FIN) AF: 0.437 AC: 4615 AN: 10556

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29168 AN: 67950

Other (OTH) AF: 0.401 AC: 847 AN: 2112

Alfa AF: 0.249 Hom.: 423

Bravo AF: 0.454

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.81
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism

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