rs75617873

Variant names:

• chr22-44130225-A-C
• rs75617873
• NM_013327.5:c.377-1262A>C

Your query was ambiguous. Multiple possible variants found:

• chr22-44130225-A-C
• chr22-44130225-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_013327.5(PARVB):​c.377-1262A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,344 control chromosomes in the GnomAD database, including 53 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 0.023 (53 hom., cov: 33)
• Consequence: PARVB NM_013327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783
• Publications: 9 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=-0.92).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0229 (3486/152344) while in subpopulation AFR AF = 0.0262 (1089/41570). AF 95% confidence interval is 0.025. There are 53 homozygotes in GnomAd4. There are 1571 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVB	NM_013327.5	c.377-1262A>C		intron_variant	Intron 4 of 12	ENST00000338758.12	NP_037459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVB	ENST00000338758.12	c.377-1262A>C		intron_variant	Intron 4 of 12	1	NM_013327.5	ENSP00000342492.6

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3481 AN: 152226 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0260

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00800

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0229 AC: 3486 AN: 152344 Hom.: 53 Cov.: 33 AF XY: 0.0211 AC XY: 1571 AN XY: 74504

African (AFR) AF: 0.0262 AC: 1089 AN: 41570

American (AMR) AF: 0.0260 AC: 398 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4832

European-Finnish (FIN) AF: 0.00800 AC: 85 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0260 AC: 1767 AN: 68036

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.0249 Hom.: 79

Bravo AF: 0.0241

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.43
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism

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: rs75617873; hg19: chr22-44526105;