chr12-42235748-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190980.3. 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
	YAF2	NM_005748.6	MANE Select	c.152+1851A>G		intron	N/A	NP_005739.2	Q8IY57-1
	YAF2	NM_001190980.3		c.*48A>G		3_prime_UTR	Exon 3 of 3	NP_001177909.1	Q8IY57-4
	YAF2	NM_001190979.3		c.152+1851A>G		intron	N/A	NP_001177908.1	Q8IY57-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAF2	ENST00000534854.7	TSL:1 MANE Select	c.152+1851A>G		intron	N/A	ENSP00000439256.2	Q8IY57-1
	YAF2	ENST00000327791.8	TSL:1	c.152+1851A>G		intron	N/A	ENSP00000328004.5	Q8IY57-5
	YAF2	ENST00000555248.2	TSL:2	c.*48A>G		3_prime_UTR	Exon 3 of 3	ENSP00000451626.2	Q8IY57-4

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

GnomAD2 exomes AF: 0.690 AC: 92651 AN: 134222 AF XY: 0.693

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 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

African (AFR) AF: 0.946 AC: 29843 AN: 31546

American (AMR) AF: 0.641 AC: 22852 AN: 35666

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 16366 AN: 25170

East Asian (EAS) AF: 0.790 AC: 28241 AN: 35728

South Asian (SAS) AF: 0.780 AC: 61700 AN: 79066

European-Finnish (FIN) AF: 0.606 AC: 20494 AN: 33842

Middle Eastern (MID) AF: 0.694 AC: 3731 AN: 5376

European-Non Finnish (NFE) AF: 0.641 AC: 690886 AN: 1078630

Other (OTH) AF: 0.684 AC: 39559 AN: 57816

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

African (AFR) AF: 0.938 AC: 38864 AN: 41454

American (AMR) AF: 0.696 AC: 10628 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2277 AN: 3466

East Asian (EAS) AF: 0.826 AC: 4266 AN: 5164

South Asian (SAS) AF: 0.795 AC: 3839 AN: 4826

European-Finnish (FIN) AF: 0.614 AC: 6453 AN: 10504

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 42957 AN: 67888

Other (OTH) AF: 0.724 AC: 1528 AN: 2110

Alfa AF: 0.666 Hom.: 18884

Bravo AF: 0.746

Asia WGS AF: 0.798 AC: 2773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7960176; hg19: chr12-42629550;