rs632610

chr12-133084132-A-Gchr12-133084132-A-T

Variant summary

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

The NM_003440.4(ZNF140):c.232+571A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 421,634 control chromosomes in the GnomAD database, including 51,138 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 0.44 (16003 hom., cov: 31)
  • Exomes 𝑓: 0.50 (35135 hom.)
• Consequence: ZNF140 NM_003440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

Genes affected

ZNF140 (HGNC:12925): (zinc finger protein 140) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF140	NM_003440.4	c.232+571A>G		intron_variant		ENST00000355557.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF140	ENST00000355557.7	c.232+571A>G		intron_variant		1	NM_003440.4	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 65983 AN: 151350 Hom.: 15997 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.501 AC: 135334 AN: 270166 Hom.: 35135 Cov.: 0 AF XY: 0.504 AC XY: 78527 AN XY: 155712

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.637

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.769

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.457

Gnomad4 NFE exome AF: 0.477

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.436 AC: 66006 AN: 151468 Hom.: 16003 Cov.: 31 AF XY: 0.442 AC XY: 32726 AN XY: 73992

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.505

Alfa AF: 0.428 Hom.: 1985

Bravo AF: 0.439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.5
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs632610; hg19: chr12-133660718; COSMIC: COSV60579664;