NM_013327.5:c.*2877A>G

Variant names:

• chr22-44171555-A-G
• rs9614207
• NM_013327.5:c.*2877A>G

Variant summary

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

The NM_013327.5(PARVB):​c.*2877A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,580 control chromosomes in the GnomAD database, including 8,889 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 0.34 (8881 hom., cov: 29)
  • Exomes 𝑓: 0.23 (8 hom.)
• Consequence: PARVB NM_013327.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013327.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	NM_013327.5	MANE Select	c.*2877A>G		3_prime_UTR	Exon 13 of 13	NP_037459.2
	PARVB	NM_001003828.3		c.*2877A>G		3_prime_UTR	Exon 14 of 14	NP_001003828.1
	PARVB	NM_001243385.2		c.*2877A>G		3_prime_UTR	Exon 13 of 13	NP_001230314.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000338758.12	TSL:1 MANE Select	c.*2877A>G		3_prime_UTR	Exon 13 of 13	ENSP00000342492.6

Frequencies

GnomAD3 genomes AF: 0.337 AC: 50960 AN: 151242 Hom.: 8872 Cov.: 29

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.234 AC: 52 AN: 222 Hom.: 8 Cov.: 0 AF XY: 0.250 AC XY: 40 AN XY: 160

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.375 AC: 3 AN: 8

South Asian (SAS) AF: 0.154 AC: 4 AN: 26

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.244 AC: 40 AN: 164

Other (OTH) AF: 0.250 AC: 4 AN: 16

GnomAD4 genome AF: 0.337 AC: 50995 AN: 151358 Hom.: 8881 Cov.: 29 AF XY: 0.332 AC XY: 24492 AN XY: 73880

African (AFR) AF: 0.291 AC: 11994 AN: 41268

American (AMR) AF: 0.426 AC: 6475 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1165 AN: 3466

East Asian (EAS) AF: 0.188 AC: 966 AN: 5130

South Asian (SAS) AF: 0.167 AC: 807 AN: 4818

European-Finnish (FIN) AF: 0.292 AC: 3010 AN: 10298

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25437 AN: 67878

Other (OTH) AF: 0.345 AC: 724 AN: 2100

Alfa AF: 0.361 Hom.: 41249

Bravo AF: 0.346

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs9614207; hg19: chr22-44567435;