rs10500758

Variant names:

• chr11-12523822-A-G
• rs10500758
• NM_018222.5:c.1043-4027A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-12523822-A-G
• chr11-12523822-A-T

Variant summary

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

The NM_018222.5(PARVA):​c.1043-4027A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 152,308 control chromosomes in the GnomAD database, including 292 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 0.038 (292 hom., cov: 33)
• Consequence: PARVA NM_018222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARVA	NM_018222.5	c.1043-4027A>G		intron_variant	Intron 12 of 12	ENST00000334956.15	NP_060692.3
PARVA	XM_005253015.4	c.911-4027A>G		intron_variant	Intron 12 of 12		XP_005253072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARVA	ENST00000334956.15	c.1043-4027A>G		intron_variant	Intron 12 of 12	1	NM_018222.5	ENSP00000334008.9

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5787 AN: 152190 Hom.: 290 Cov.: 33

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0380 AC: 5786 AN: 152308 Hom.: 292 Cov.: 33 AF XY: 0.0430 AC XY: 3201 AN XY: 74476

African (AFR) AF: 0.0201 AC: 836 AN: 41570

American (AMR) AF: 0.0734 AC: 1124 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1096 AN: 5170

South Asian (SAS) AF: 0.135 AC: 654 AN: 4830

European-Finnish (FIN) AF: 0.0284 AC: 302 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1667 AN: 68014

Other (OTH) AF: 0.0350 AC: 74 AN: 2114

Alfa AF: 0.0251 Hom.: 105

Bravo AF: 0.0390

Asia WGS AF: 0.171 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.20
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: rs10500758; hg19: chr11-12545369;