rs4375421

Positions:

• chr11-12414056-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018222.5(PARVA):​c.136+36273G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,044 control chromosomes in the GnomAD database, including 6,034 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 0.28 (6034 hom., cov: 33)
• Consequence: PARVA NM_018222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

PARVA (HGNC:14652): (parvin alpha) This gene encodes a member of the parvin family of actin-binding proteins. Parvins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. The encoded protein is part of the integrin-linked kinase signaling complex and plays a role in cell adhesion, motility and survival. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARVA	NM_018222.5	c.136+36273G>A		intron_variant		ENST00000334956.15	NP_060692.3
PARVA	XM_005253015.4	c.4+37322G>A		intron_variant			XP_005253072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARVA	ENST00000334956.15	c.136+36273G>A		intron_variant		1	NM_018222.5	ENSP00000334008	P1
PARVA	ENST00000530755.5	n.221+36273G>A		intron_variant, non_coding_transcript_variant		2
PARVA	ENST00000533345.5	n.113+15703G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41963 AN: 151926 Hom.: 6029 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.276 AC: 41988 AN: 152044 Hom.: 6034 Cov.: 33 AF XY: 0.274 AC XY: 20366 AN XY: 74292

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.290

Alfa AF: 0.310 Hom.: 7261

Bravo AF: 0.274

Asia WGS AF: 0.158 AC: 554 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	0.034
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs4375421; hg19: chr11-12435603;