12-42235748-T-C

Variant names:

• chr12-42235748-T-C
• rs7960176
• NM_005748.6:c.152+1851A>G

Variant summary

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

The NM_001190980.3(YAF2):​c.*48A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,534,714 control chromosomes in the GnomAD database, including 347,638 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 0.73 (42439 hom., cov: 30)
  • Exomes 𝑓: 0.66 (305199 hom.)
• Consequence: YAF2 NM_001190980.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

Genes affected

YAF2 (HGNC:17363): (YY1 associated factor 2) This gene encodes a zinc finger containing protein that functions in the regulation of transcription. This protein was identified as an interacting partner of transcriptional repressor protein Yy1, and also interacts with other transcriptional regulators, including Myc and Polycomb. This protein can promote proteolysis of Yy1. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAF2	NM_005748.6	c.152+1851A>G		intron_variant	Intron 2 of 3	ENST00000534854.7	NP_005739.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YAF2	ENST00000534854.7	c.152+1851A>G		intron_variant	Intron 2 of 3	1	NM_005748.6	ENSP00000439256.2

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111456 AN: 151758 Hom.: 42382 Cov.: 30

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.723

GnomAD3 exomes AF: 0.690 AC: 92651 AN: 134222 Hom.: 32531 AF XY: 0.693 AC XY: 50701 AN XY: 73120

Gnomad AFR exome AF: 0.942

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.651

Gnomad EAS exome AF: 0.834

Gnomad SAS exome AF: 0.777

Gnomad FIN exome AF: 0.604

Gnomad NFE exome AF: 0.640

Gnomad OTH exome AF: 0.669

GnomAD4 exome AF: 0.661 AC: 913672 AN: 1382840 Hom.: 305199 Cov.: 53 AF XY: 0.663 AC XY: 452564 AN XY: 682374

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.780

Gnomad4 FIN exome AF: 0.606

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.684

GnomAD4 genome AF: 0.735 AC: 111573 AN: 151874 Hom.: 42439 Cov.: 30 AF XY: 0.736 AC XY: 54613 AN XY: 74210

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.724

Alfa AF: 0.666 Hom.: 16955

Bravo AF: 0.746

Asia WGS AF: 0.798 AC: 2773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs7960176; hg19: chr12-42629550;