chr22-44094016-T-C

Variant names:

• chr22-44094016-T-C
• rs738479
• NM_013327.5:c.201T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013327.5(PARVB):​c.201T>C​(p.Leu67Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 1,589,898 control chromosomes in the GnomAD database, including 285,856 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27430 hom., cov: 33)
  • Exomes 𝑓: 0.60 (258426 hom.)
• Consequence: PARVB NM_013327.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.00001724
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• Publications: 21 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.487 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	NM_013327.5	MANE Select	c.201T>C	p.Leu67Leu	splice_region synonymous	Exon 2 of 13	NP_037459.2
	PARVB	NM_001003828.3		c.300T>C	p.Leu100Leu	splice_region synonymous	Exon 3 of 14	NP_001003828.1
	PARVB	NM_001243385.2		c.90T>C	p.Leu30Leu	splice_region synonymous	Exon 2 of 13	NP_001230314.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVB	ENST00000338758.12	TSL:1 MANE Select	c.201T>C	p.Leu67Leu	splice_region synonymous	Exon 2 of 13	ENSP00000342492.6
	PARVB	ENST00000406477.7	TSL:1	c.300T>C	p.Leu100Leu	splice_region synonymous	Exon 3 of 14	ENSP00000384515.3
	PARVB	ENST00000404989.1	TSL:1	c.90T>C	p.Leu30Leu	splice_region synonymous	Exon 2 of 13	ENSP00000384353.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90736 AN: 152042 Hom.: 27404 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.562

GnomAD2 exomes AF: 0.619 AC: 154654 AN: 249718 AF XY: 0.613

Gnomad AFR exome AF: 0.592

Gnomad AMR exome AF: 0.688

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.862

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.596 AC: 856986 AN: 1437738 Hom.: 258426 Cov.: 27 AF XY: 0.595 AC XY: 426504 AN XY: 716754

African (AFR) AF: 0.594 AC: 19513 AN: 32840

American (AMR) AF: 0.675 AC: 30008 AN: 44428

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 14316 AN: 25906

East Asian (EAS) AF: 0.863 AC: 34166 AN: 39572

South Asian (SAS) AF: 0.600 AC: 51333 AN: 85578

European-Finnish (FIN) AF: 0.575 AC: 30628 AN: 53292

Middle Eastern (MID) AF: 0.526 AC: 3000 AN: 5700

European-Non Finnish (NFE) AF: 0.585 AC: 637977 AN: 1090816

Other (OTH) AF: 0.605 AC: 36045 AN: 59606

GnomAD4 genome AF: 0.597 AC: 90798 AN: 152160 Hom.: 27430 Cov.: 33 AF XY: 0.600 AC XY: 44621 AN XY: 74388

African (AFR) AF: 0.589 AC: 24435 AN: 41518

American (AMR) AF: 0.625 AC: 9565 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1910 AN: 3470

East Asian (EAS) AF: 0.863 AC: 4459 AN: 5166

South Asian (SAS) AF: 0.617 AC: 2972 AN: 4820

European-Finnish (FIN) AF: 0.588 AC: 6222 AN: 10586

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39367 AN: 67994

Other (OTH) AF: 0.564 AC: 1193 AN: 2114

Alfa AF: 0.588 Hom.: 92583

Bravo AF: 0.603

Asia WGS AF: 0.740 AC: 2572 AN: 3478

EpiCase AF: 0.567

EpiControl AF: 0.569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.67
DANN	Benign	0.55
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=66/34	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0040
Splicevardb		2.0
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: rs738479; hg19: chr22-44489896; COSMIC: COSV58689553;