chr22-44142808-T-C

Variant names:

• chr22-44142808-T-C
• rs2267617
• NM_013327.5:c.712+2665T>C

Variant summary

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

The NM_001003828.3(PARVB):​c.811+2665T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,138 control chromosomes in the GnomAD database, including 15,520 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 0.43 (15516 hom., cov: 33)
  • Exomes 𝑓: 0.72 (4 hom.)
• Consequence: PARVB NM_001003828.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239
• 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]

ENSG00000280434 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	NM_013327.5	MANE Select	c.712+2665T>C		intron	N/A	NP_037459.2
	PARVB	NM_001003828.3		c.811+2665T>C		intron	N/A	NP_001003828.1
	PARVB	NM_001243385.2		c.601+2665T>C		intron	N/A	NP_001230314.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000338758.12	TSL:1 MANE Select	c.712+2665T>C		intron	N/A	ENSP00000342492.6
	PARVB	ENST00000406477.7	TSL:1	c.811+2665T>C		intron	N/A	ENSP00000384515.3
	PARVB	ENST00000404989.1	TSL:1	c.601+2665T>C		intron	N/A	ENSP00000384353.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66103 AN: 152002 Hom.: 15498 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.722 AC: 13 AN: 18 Hom.: 4 Cov.: 0 AF XY: 0.750 AC XY: 9 AN XY: 12

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: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 7 AN: 10

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.435 AC: 66149 AN: 152120 Hom.: 15516 Cov.: 33 AF XY: 0.437 AC XY: 32505 AN XY: 74368

African (AFR) AF: 0.245 AC: 10148 AN: 41476

American (AMR) AF: 0.475 AC: 7261 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1526 AN: 3468

East Asian (EAS) AF: 0.564 AC: 2913 AN: 5168

South Asian (SAS) AF: 0.413 AC: 1991 AN: 4824

European-Finnish (FIN) AF: 0.568 AC: 6017 AN: 10594

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34724 AN: 67984

Other (OTH) AF: 0.455 AC: 960 AN: 2112

Alfa AF: 0.482 Hom.: 15031

Bravo AF: 0.422

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.72
PhyloP100		-0.24
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: rs2267617; hg19: chr22-44538688;