2-48440812-CGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr2-48440812-C-CGCGGCGGCGGCG
• rs34664331
• NM_001135629.3:c.-130_-119dupGGCGGCGGCGGC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001135629.3(PPP1R21):​c.-130_-119dupGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 626,748 control chromosomes in the GnomAD database, including 12 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00056 (7 hom., cov: 24)
  • Exomes 𝑓: 0.00041 (5 hom.)
• Consequence: PPP1R21 NM_001135629.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000561 (85/151632) while in subpopulation AMR AF = 0.00256 (39/15250). AF 95% confidence interval is 0.00192. There are 7 homozygotes in GnomAd4. There are 28 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R21	NM_001135629.3	c.-130_-119dupGGCGGCGGCGGC		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.-130_-119dupGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 22	1	NM_001135629.3	ENSP00000294952.8

Frequencies

GnomAD3 genomes AF: 0.000561 AC: 85 AN: 151514 Hom.: 7 Cov.: 24

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00236

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.000408 AC: 194 AN: 475116 Hom.: 5 Cov.: 4 AF XY: 0.000449 AC XY: 115 AN XY: 255926

African (AFR) AF: 0.000299 AC: 3 AN: 10020

American (AMR) AF: 0.000278 AC: 5 AN: 17980

Ashkenazi Jewish (ASJ) AF: 0.000201 AC: 3 AN: 14962

East Asian (EAS) AF: 0.00123 AC: 31 AN: 25270

South Asian (SAS) AF: 0.000905 AC: 45 AN: 49734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42394

Middle Eastern (MID) AF: 0.000951 AC: 2 AN: 2102

European-Non Finnish (NFE) AF: 0.000182 AC: 52 AN: 286222

Other (OTH) AF: 0.00201 AC: 53 AN: 26432

GnomAD4 genome AF: 0.000561 AC: 85 AN: 151632 Hom.: 7 Cov.: 24 AF XY: 0.000378 AC XY: 28 AN XY: 74110

African (AFR) AF: 0.000434 AC: 18 AN: 41454

American (AMR) AF: 0.00256 AC: 39 AN: 15250

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

East Asian (EAS) AF: 0.00236 AC: 12 AN: 5076

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

European-Finnish (FIN) AF: 0.0000953 AC: 1 AN: 10492

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

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67764

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00 Hom.: 56

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=300/0	polymorphism

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;