chr15-64155818-A-AT

Variant names:

• chr15-64155818-A-AT
• rs202080377
• NM_000942.5:c.*204dupA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000942.5(PPIB):​c.*204dupA variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 511,490 control chromosomes in the GnomAD database, including 391 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (189 hom., cov: 26)
  • Exomes 𝑓: 0.057 (202 hom.)
• Consequence: PPIB NM_000942.5 splice_region
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.514
• Publications: 0 publications found

Genes affected

PPIB (HGNC:9255): (peptidylprolyl isomerase B) The protein encoded by this gene is a cyclosporine-binding protein and is mainly located within the endoplasmic reticulum. It is associated with the secretory pathway and released in biological fluids. This protein can bind to cells derived from T- and B-lymphocytes, and may regulate cyclosporine A-mediated immunosuppression. Variants have been identified in this protein that give rise to recessive forms of osteogenesis imperfecta. [provided by RefSeq, Oct 2009]

SNX22 (HGNC:16315): (sorting nexin 22) The protein encoded by this gene is a sorting nexin that is found in the cytoplasm, where it interacts with membrane-bound phosphatidylinositol 3-phosphate. The encoded protein may play a role in intracellular trafficking. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 15-64155818-A-AT is Benign according to our data. Variant chr15-64155818-A-AT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 316695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000942.5. 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
	PPIB	NM_000942.5	MANE Select	c.*204dupA		splice_region	Exon 5 of 5	NP_000933.1	P23284
	PPIB	NM_000942.5	MANE Select	c.*204dupA		3_prime_UTR	Exon 5 of 5	NP_000933.1	P23284
	SNX22	NM_024798.3	MANE Select	c.*1312dupT		3_prime_UTR	Exon 7 of 7	NP_079074.2	Q96L94-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIB	ENST00000300026.4	TSL:1 MANE Select	c.*204dupA		splice_region	Exon 5 of 5	ENSP00000300026.4	P23284
	PPIB	ENST00000300026.4	TSL:1 MANE Select	c.*204dupA		3_prime_UTR	Exon 5 of 5	ENSP00000300026.4	P23284
	SNX22	ENST00000325881.9	TSL:1 MANE Select	c.*1312dupT		3_prime_UTR	Exon 7 of 7	ENSP00000323435.4	Q96L94-1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 6601 AN: 65158 Hom.: 189 Cov.: 26

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.00337

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.0984

GnomAD4 exome AF: 0.0572 AC: 25537 AN: 446274 Hom.: 202 Cov.: 7 AF XY: 0.0591 AC XY: 13923 AN XY: 235716

African (AFR) AF: 0.00879 AC: 108 AN: 12288

American (AMR) AF: 0.0256 AC: 438 AN: 17116

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 1176 AN: 12360

East Asian (EAS) AF: 0.000129 AC: 3 AN: 23332

South Asian (SAS) AF: 0.0809 AC: 3802 AN: 47008

European-Finnish (FIN) AF: 0.0675 AC: 1464 AN: 21694

Middle Eastern (MID) AF: 0.0979 AC: 176 AN: 1798

European-Non Finnish (NFE) AF: 0.0595 AC: 17099 AN: 287166

Other (OTH) AF: 0.0541 AC: 1271 AN: 23512

GnomAD4 genome AF: 0.101 AC: 6593 AN: 65216 Hom.: 189 Cov.: 26 AF XY: 0.103 AC XY: 3244 AN XY: 31498

African (AFR) AF: 0.0136 AC: 435 AN: 32082

American (AMR) AF: 0.0929 AC: 402 AN: 4328

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 359 AN: 1992

East Asian (EAS) AF: 0.00336 AC: 2 AN: 596

South Asian (SAS) AF: 0.124 AC: 403 AN: 3242

European-Finnish (FIN) AF: 0.329 AC: 662 AN: 2010

Middle Eastern (MID) AF: 0.0682 AC: 9 AN: 132

European-Non Finnish (NFE) AF: 0.214 AC: 4195 AN: 19594

Other (OTH) AF: 0.0986 AC: 86 AN: 872

Alfa AF: 0.0452 Hom.: 2

Asia WGS AF: 0.0280 AC: 99 AN: 3440

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Osteogenesis Imperfecta, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51
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: rs202080377; hg19: chr15-64448017;