NM_013327.5:c.273+914A>G

Variant names:

• chr22-44101037-A-G
• rs8140244
• NM_013327.5:c.273+914A>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.273+914A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,180 control chromosomes in the GnomAD database, including 6,958 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 0.26 (6958 hom., cov: 32)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	NM_013327.5	MANE Select	c.273+914A>G		intron	N/A	NP_037459.2
	PARVB	NM_001003828.3		c.372+914A>G		intron	N/A	NP_001003828.1	Q9HBI1-2
	PARVB	NM_001243385.2		c.162+914A>G		intron	N/A	NP_001230314.1	Q9HBI1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000338758.12	TSL:1 MANE Select	c.273+914A>G		intron	N/A	ENSP00000342492.6	Q9HBI1-1
	PARVB	ENST00000406477.7	TSL:1	c.372+914A>G		intron	N/A	ENSP00000384515.3	Q9HBI1-2
	PARVB	ENST00000404989.1	TSL:1	c.162+914A>G		intron	N/A	ENSP00000384353.1	Q9HBI1-3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39997 AN: 152062 Hom.: 6943 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 40067 AN: 152180 Hom.: 6958 Cov.: 32 AF XY: 0.262 AC XY: 19483 AN XY: 74406

African (AFR) AF: 0.500 AC: 20735 AN: 41490

American (AMR) AF: 0.193 AC: 2956 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3468

East Asian (EAS) AF: 0.118 AC: 610 AN: 5178

South Asian (SAS) AF: 0.165 AC: 796 AN: 4820

European-Finnish (FIN) AF: 0.193 AC: 2043 AN: 10598

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11293 AN: 68008

Other (OTH) AF: 0.241 AC: 509 AN: 2114

Alfa AF: 0.200 Hom.: 11419

Bravo AF: 0.272

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.084
DANN	Benign	0.48
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8140244; hg19: chr22-44496917;