22-21732084-T-C

Variant names:

• chr22-21732084-T-C
• rs4821217
• NM_013313.5:c.-165+3531A>G

Variant summary

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

The NM_013313.5(YPEL1):​c.-165+3531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,268 control chromosomes in the GnomAD database, including 65,033 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 0.92 (65033 hom., cov: 33)
• Consequence: YPEL1 NM_013313.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 6 publications found

Genes affected

YPEL1 (HGNC:12845): (yippee like 1) This gene is located in the region associated with DiGeorge syndrome on chromosome 22. The encoded protein localizes to the centrosome and nucleolus and may play a role in the regulation of cell division. [provided by RefSeq, Feb 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013313.5. 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
	YPEL1	NM_013313.5	MANE Select	c.-165+3531A>G		intron	N/A	NP_037445.1	O60688
	YPEL1	NR_130910.2		n.180+3531A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YPEL1	ENST00000339468.8	TSL:1 MANE Select	c.-165+3531A>G		intron	N/A	ENSP00000342832.3	O60688
	YPEL1	ENST00000403503.1	TSL:3	c.-165+3531A>G		intron	N/A	ENSP00000386014.1	B5MCX2
	YPEL1	ENST00000477675.1	TSL:2	n.147+3531A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140077 AN: 152150 Hom.: 64984 Cov.: 33

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.902

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.921 AC: 140182 AN: 152268 Hom.: 65033 Cov.: 33 AF XY: 0.915 AC XY: 68102 AN XY: 74446

African (AFR) AF: 0.969 AC: 40290 AN: 41558

American (AMR) AF: 0.793 AC: 12116 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3054 AN: 3472

East Asian (EAS) AF: 0.661 AC: 3407 AN: 5152

South Asian (SAS) AF: 0.879 AC: 4247 AN: 4830

European-Finnish (FIN) AF: 0.907 AC: 9630 AN: 10620

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64369 AN: 68032

Other (OTH) AF: 0.903 AC: 1910 AN: 2114

Alfa AF: 0.926 Hom.: 102151

Bravo AF: 0.910

Asia WGS AF: 0.801 AC: 2787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.055
DANN	Benign	0.76
PhyloP100		-2.0
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: rs4821217; hg19: chr22-22086373;