rs2281292

chr22-43999509-A-Cchr22-43999509-A-G

Variant summary

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

The ENST00000406477.7(PARVB):c.72-25A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,560,994 control chromosomes in the GnomAD database, including 136,451 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 0.47 (17494 hom., cov: 32)
  • Exomes 𝑓: 0.41 (118957 hom.)
• Consequence: PARVB ENST00000406477.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

Genes affected

PARVB (HGNC:14653): (parvin beta) This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

SAMM50 (HGNC:24276): (SAMM50 sorting and assembly machinery component) This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.[provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARVB	NM_001003828.3	c.72-25A>C		intron_variant
PARVB	XM_024452236.2	c.72-25A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARVB	ENST00000406477.7	c.72-25A>C		intron_variant		1
SAMM50	ENST00000465768.1	n.79+9103A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71531 AN: 151816 Hom.: 17487 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.458

GnomAD3 exomes AF: 0.439 AC: 108533 AN: 247278 Hom.: 24383 AF XY: 0.436 AC XY: 58562 AN XY: 134304

Gnomad AFR exome AF: 0.617

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.488

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.407 AC: 574137 AN: 1409062 Hom.: 118957 Cov.: 23 AF XY: 0.409 AC XY: 287897 AN XY: 703908

Gnomad4 AFR exome AF: 0.611

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.389

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.471 AC: 71563 AN: 151932 Hom.: 17494 Cov.: 32 AF XY: 0.475 AC XY: 35229 AN XY: 74234

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.454

Alfa AF: 0.414 Hom.: 6949

Bravo AF: 0.477

Asia WGS AF: 0.482 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.18
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2281292; hg19: chr22-44395389; COSMIC: COSV63109517; COSMIC: COSV63109517;