chr2-48440812-CGCGGCGGCG-C

Variant names:

• chr2-48440812-CGCGGCGGCG-C
• rs34664331
• NM_001135629.3:c.-127_-119delGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001135629.3(PPP1R21):​c.-127_-119delGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 626,736 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: PPP1R21 NM_001135629.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• Publications: 4 publications found

Genes affected

PPP1R21 (HGNC:30595): (protein phosphatase 1 regulatory subunit 21) Located in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

PPP1R21-DT (HGNC:55206): (PPP1R21 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00058 (88/151630) while in subpopulation AFR AF = 0.00191 (79/41452). AF 95% confidence interval is 0.00157. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R21	NM_001135629.3	c.-127_-119delGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 22	ENST00000294952.13	NP_001129101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R21	ENST00000294952.13	c.-127_-119delGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_001135629.3	ENSP00000294952.8

Frequencies

GnomAD3 genomes AF: 0.000574 AC: 87 AN: 151512 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000141 AC: 67 AN: 475106 Hom.: 0 AF XY: 0.000148 AC XY: 38 AN XY: 255920

African (AFR) AF: 0.00180 AC: 18 AN: 10020

American (AMR) AF: 0.000222 AC: 4 AN: 17978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14962

East Asian (EAS) AF: 0.0000792 AC: 2 AN: 25268

South Asian (SAS) AF: 0.000121 AC: 6 AN: 49730

European-Finnish (FIN) AF: 0.0000708 AC: 3 AN: 42394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2102

European-Non Finnish (NFE) AF: 0.0000978 AC: 28 AN: 286220

Other (OTH) AF: 0.000227 AC: 6 AN: 26432

GnomAD4 genome AF: 0.000580 AC: 88 AN: 151630 Hom.: 0 Cov.: 24 AF XY: 0.000499 AC XY: 37 AN XY: 74110

African (AFR) AF: 0.00191 AC: 79 AN: 41452

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5076

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67764

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000174 Hom.: 56

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34664331; hg19: chr2-48667951;