rs632610

Variant names:

• chr12-133084132-A-G
• rs632610
• NM_003440.4:c.232+571A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-133084132-A-G
• chr12-133084132-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.01).
• 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 rank	MANE	Protein	UniProt
ZNF140	NM_003440.4	c.232+571A>G		intron_variant	Intron 4 of 4	ENST00000355557.7	NP_003431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF140	ENST00000355557.7	c.232+571A>G		intron_variant	Intron 4 of 4	1	NM_003440.4	ENSP00000347755.2

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

African (AFR) AF: 0.218 AC: 1347 AN: 6180

American (AMR) AF: 0.637 AC: 11402 AN: 17900

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 5285 AN: 9436

East Asian (EAS) AF: 0.769 AC: 6376 AN: 8290

South Asian (SAS) AF: 0.509 AC: 26485 AN: 51990

European-Finnish (FIN) AF: 0.457 AC: 5441 AN: 11904

Middle Eastern (MID) AF: 0.580 AC: 1511 AN: 2604

European-Non Finnish (NFE) AF: 0.477 AC: 71101 AN: 149134

Other (OTH) AF: 0.502 AC: 6386 AN: 12728

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

African (AFR) AF: 0.223 AC: 9208 AN: 41228

American (AMR) AF: 0.588 AC: 8966 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1957 AN: 3460

East Asian (EAS) AF: 0.778 AC: 4006 AN: 5152

South Asian (SAS) AF: 0.518 AC: 2490 AN: 4806

European-Finnish (FIN) AF: 0.461 AC: 4801 AN: 10412

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.484 AC: 32859 AN: 67846

Other (OTH) AF: 0.505 AC: 1061 AN: 2100

Alfa AF: 0.358 Hom.: 2598

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
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs632610; hg19: chr12-133660718; COSMIC: COSV60579664;