rs2281292

Variant names:

• chr22-43999509-A-C
• rs2281292
• ENST00000406477.7:c.72-25A>C

Your query was ambiguous. Multiple possible variants found:

• chr22-43999509-A-C
• chr22-43999509-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003828.3(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 NM_001003828.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003828.3. 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
	PARVB	NM_001003828.3		c.72-25A>C		intron	N/A	NP_001003828.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000406477.7	TSL:1	c.72-25A>C		intron	N/A	ENSP00000384515.3
	SAMM50	ENST00000465768.1	TSL:3	n.79+9103A>C		intron	N/A

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

GnomAD2 exomes AF: 0.439 AC: 108533 AN: 247278 AF XY: 0.436

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 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

African (AFR) AF: 0.611 AC: 19808 AN: 32416

American (AMR) AF: 0.440 AC: 19572 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9192 AN: 25780

East Asian (EAS) AF: 0.495 AC: 19549 AN: 39464

South Asian (SAS) AF: 0.467 AC: 39798 AN: 85136

European-Finnish (FIN) AF: 0.469 AC: 25016 AN: 53370

Middle Eastern (MID) AF: 0.443 AC: 2515 AN: 5680

European-Non Finnish (NFE) AF: 0.389 AC: 414434 AN: 1064200

Other (OTH) AF: 0.414 AC: 24253 AN: 58556

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

African (AFR) AF: 0.607 AC: 25154 AN: 41426

American (AMR) AF: 0.464 AC: 7084 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2518 AN: 5154

South Asian (SAS) AF: 0.474 AC: 2281 AN: 4812

European-Finnish (FIN) AF: 0.472 AC: 4976 AN: 10552

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26695 AN: 67948

Other (OTH) AF: 0.454 AC: 956 AN: 2108

Alfa AF: 0.419 Hom.: 24958

Bravo AF: 0.477

Asia WGS AF: 0.482 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.59
PhyloP100		-0.23
PromoterAI		-0.0062	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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