chr5-43161235-A-G

Variant names:

• chr5-43161235-A-G
• rs903391
• NM_001330707.2:c.372-14A>G

Variant summary

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

The NM_001330707.2(ZNF131):​c.372-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,576,526 control chromosomes in the GnomAD database, including 64,032 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 0.27 (6295 hom., cov: 32)
  • Exomes 𝑓: 0.27 (57737 hom.)
• Consequence: ZNF131 NM_001330707.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 9 publications found

Genes affected

ZNF131 (HGNC:12915): (zinc finger protein 131) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Located in intermediate filament cytoskeleton and nucleoplasm. [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 (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330707.2. 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
	ZNF131	NM_001330707.2	MANE Select	c.372-14A>G		intron	N/A	NP_001317636.1
	ZNF131	NM_001297548.3		c.372-14A>G		intron	N/A	NP_001284477.1
	ZNF131	NM_001330708.2		c.372-14A>G		intron	N/A	NP_001317637.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF131	ENST00000682664.1	MANE Select	c.372-14A>G		intron	N/A	ENSP00000507111.1
	ZNF131	ENST00000515326.5	TSL:1	c.372-14A>G		intron	N/A	ENSP00000422079.1
	ZNF131	ENST00000507218.5	TSL:1	n.227-14A>G		intron	N/A	ENSP00000425139.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41643 AN: 152030 Hom.: 6286 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.269

GnomAD2 exomes AF: 0.313 AC: 68775 AN: 219994 AF XY: 0.306

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.646

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.274 AC: 390923 AN: 1424378 Hom.: 57737 Cov.: 32 AF XY: 0.275 AC XY: 194061 AN XY: 706208

African (AFR) AF: 0.244 AC: 7661 AN: 31402

American (AMR) AF: 0.414 AC: 14888 AN: 35922

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 5941 AN: 24244

East Asian (EAS) AF: 0.642 AC: 25315 AN: 39420

South Asian (SAS) AF: 0.329 AC: 25970 AN: 78886

European-Finnish (FIN) AF: 0.260 AC: 13613 AN: 52332

Middle Eastern (MID) AF: 0.240 AC: 1338 AN: 5568

European-Non Finnish (NFE) AF: 0.255 AC: 279710 AN: 1097892

Other (OTH) AF: 0.281 AC: 16487 AN: 58712

GnomAD4 genome AF: 0.274 AC: 41674 AN: 152148 Hom.: 6295 Cov.: 32 AF XY: 0.279 AC XY: 20752 AN XY: 74404

African (AFR) AF: 0.240 AC: 9955 AN: 41484

American (AMR) AF: 0.362 AC: 5532 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3470

East Asian (EAS) AF: 0.632 AC: 3269 AN: 5176

South Asian (SAS) AF: 0.347 AC: 1674 AN: 4818

European-Finnish (FIN) AF: 0.253 AC: 2682 AN: 10608

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16960 AN: 68000

Other (OTH) AF: 0.271 AC: 573 AN: 2114

Alfa AF: 0.253 Hom.: 933

Bravo AF: 0.282

Asia WGS AF: 0.473 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.39
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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: rs903391; hg19: chr5-43161337; COSMIC: COSV61002651; COSMIC: COSV61002651;