22-44104263-A-G

Variant names:

• chr22-44104263-A-G
• rs2092437
• NM_013327.5:c.273+4140A>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+4140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,288 control chromosomes in the GnomAD database, including 936 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 0.091 (936 hom., cov: 33)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 5 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]

ENSG00000279175 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_013327.5	c.273+4140A>G		intron_variant	Intron 3 of 12	ENST00000338758.12	NP_037459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12	c.273+4140A>G		intron_variant	Intron 3 of 12	1	NM_013327.5	ENSP00000342492.6

Frequencies

GnomAD3 genomes AF: 0.0907 AC: 13808 AN: 152158 Hom.: 936 Cov.: 33

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.167 AC: 2 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 2 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0907 AC: 13808 AN: 152276 Hom.: 936 Cov.: 33 AF XY: 0.0858 AC XY: 6387 AN XY: 74462

African (AFR) AF: 0.0262 AC: 1088 AN: 41558

American (AMR) AF: 0.0928 AC: 1420 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0687 AC: 332 AN: 4830

European-Finnish (FIN) AF: 0.0421 AC: 447 AN: 10610

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9512 AN: 68004

Other (OTH) AF: 0.112 AC: 238 AN: 2116

Alfa AF: 0.122 Hom.: 2873

Bravo AF: 0.0927

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.76
PhyloP100		0.63
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: rs2092437; hg19: chr22-44500143;