22-21728499-C-T

Position:

• chr22-21728499-C-T

Variant summary

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

The ENST00000339468.8(YPEL1):​c.-165+7116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 152,224 control chromosomes in the GnomAD database, including 294 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 0.060 (294 hom., cov: 32)
• Consequence: YPEL1 ENST00000339468.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YPEL1	NM_013313.5	c.-165+7116G>A		intron_variant		ENST00000339468.8	NP_037445.1
YPEL1	NR_130910.2	n.180+7116G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YPEL1	ENST00000339468.8	c.-165+7116G>A		intron_variant		1	NM_013313.5	ENSP00000342832	P1
YPEL1	ENST00000403503.1	c.-165+7116G>A		intron_variant		3		ENSP00000386014
YPEL1	ENST00000477675.1	n.147+7116G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9134 AN: 152106 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0506

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0621

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

GnomAD4 genome AF: 0.0600 AC: 9140 AN: 152224 Hom.: 294 Cov.: 32 AF XY: 0.0584 AC XY: 4345 AN XY: 74432

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.0463

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.0506

Gnomad4 NFE AF: 0.0597

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0452 Hom.: 68

Bravo AF: 0.0607

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.38
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs8135616; hg19: chr22-22082788;