22-44149485-T-C

Variant names:

• chr22-44149485-T-C
• rs5764560
• NM_013327.5:c.774+1563T>C

Variant summary

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

The NM_013327.5(PARVB):​c.774+1563T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,544 control chromosomes in the GnomAD database, including 12,393 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 0.39 (12385 hom., cov: 31)
  • Exomes 𝑓: 0.37 (8 hom.)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 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.774+1563T>C		intron	N/A	NP_037459.2
	PARVB	NM_001003828.3		c.873+1563T>C		intron	N/A	NP_001003828.1	Q9HBI1-2
	PARVB	NM_001243385.2		c.663+1563T>C		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.774+1563T>C		intron	N/A	ENSP00000342492.6	Q9HBI1-1
	PARVB	ENST00000406477.7	TSL:1	c.873+1563T>C		intron	N/A	ENSP00000384515.3	Q9HBI1-2
	PARVB	ENST00000404989.1	TSL:1	c.663+1563T>C		intron	N/A	ENSP00000384353.1	Q9HBI1-3

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59070 AN: 151332 Hom.: 12381 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.367 AC: 33 AN: 90 Hom.: 8 Cov.: 0 AF XY: 0.371 AC XY: 26 AN XY: 70

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

American (AMR) AC: 0 AN: 0

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

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

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

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.391 AC: 25 AN: 64

Other (OTH) AF: 0.400 AC: 4 AN: 10

GnomAD4 genome AF: 0.390 AC: 59112 AN: 151454 Hom.: 12385 Cov.: 31 AF XY: 0.406 AC XY: 30037 AN XY: 73954

African (AFR) AF: 0.301 AC: 12450 AN: 41344

American (AMR) AF: 0.443 AC: 6755 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1524 AN: 3462

East Asian (EAS) AF: 0.788 AC: 3999 AN: 5078

South Asian (SAS) AF: 0.614 AC: 2949 AN: 4804

European-Finnish (FIN) AF: 0.491 AC: 5133 AN: 10448

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 24968 AN: 67780

Other (OTH) AF: 0.433 AC: 907 AN: 2096

Alfa AF: 0.383 Hom.: 29484

Bravo AF: 0.384

Asia WGS AF: 0.667 AC: 2316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.77
PhyloP100		0.39
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: rs5764560; hg19: chr22-44545365;