rs139096

Variant names:

• chr22-44168527-C-T
• rs139096
• NM_013327.5:c.1019-75C>T

Variant summary

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

The NM_013327.5(PARVB):​c.1019-75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 942,800 control chromosomes in the GnomAD database, including 34,544 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 0.24 (4732 hom., cov: 31)
  • Exomes 𝑓: 0.27 (29812 hom.)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 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.1019-75C>T		intron	N/A	NP_037459.2
	PARVB	NM_001003828.3		c.1118-75C>T		intron	N/A	NP_001003828.1	Q9HBI1-2
	PARVB	NM_001243385.2		c.908-75C>T		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.1019-75C>T		intron	N/A	ENSP00000342492.6	Q9HBI1-1
	PARVB	ENST00000406477.7	TSL:1	c.1118-75C>T		intron	N/A	ENSP00000384515.3	Q9HBI1-2
	PARVB	ENST00000404989.1	TSL:1	c.908-75C>T		intron	N/A	ENSP00000384353.1	Q9HBI1-3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36146 AN: 151898 Hom.: 4725 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.0895

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.266 AC: 210560 AN: 790784 Hom.: 29812 AF XY: 0.270 AC XY: 113431 AN XY: 419536

African (AFR) AF: 0.163 AC: 3361 AN: 20668

American (AMR) AF: 0.353 AC: 15229 AN: 43102

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 6461 AN: 21274

East Asian (EAS) AF: 0.0983 AC: 3597 AN: 36588

South Asian (SAS) AF: 0.338 AC: 24312 AN: 71868

European-Finnish (FIN) AF: 0.197 AC: 10303 AN: 52396

Middle Eastern (MID) AF: 0.319 AC: 1395 AN: 4378

European-Non Finnish (NFE) AF: 0.271 AC: 136015 AN: 502268

Other (OTH) AF: 0.259 AC: 9887 AN: 38242

GnomAD4 genome AF: 0.238 AC: 36162 AN: 152016 Hom.: 4732 Cov.: 31 AF XY: 0.237 AC XY: 17588 AN XY: 74286

African (AFR) AF: 0.165 AC: 6832 AN: 41476

American (AMR) AF: 0.315 AC: 4817 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1064 AN: 3468

East Asian (EAS) AF: 0.0895 AC: 464 AN: 5182

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4820

European-Finnish (FIN) AF: 0.186 AC: 1962 AN: 10536

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18562 AN: 67950

Other (OTH) AF: 0.257 AC: 541 AN: 2106

Alfa AF: 0.273 Hom.: 9635

Bravo AF: 0.243

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.6
DANN	Benign	0.54
PhyloP100		-0.38
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: rs139096; hg19: chr22-44564407; COSMIC: COSV107441705; COSMIC: COSV107441705;