11-12409179-T-C

Variant names:

• chr11-12409179-T-C
• rs1426588
• NM_018222.5:c.136+31396T>C

Variant summary

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

The NM_018222.5(PARVA):​c.136+31396T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,280 control chromosomes in the GnomAD database, including 1,067 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 0.11 (1067 hom., cov: 33)
• Consequence: PARVA NM_018222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018222.5. 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
	PARVA	NM_018222.5	MANE Select	c.136+31396T>C		intron	N/A	NP_060692.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARVA	ENST00000334956.15	TSL:1 MANE Select	c.136+31396T>C		intron	N/A	ENSP00000334008.9
	PARVA	ENST00000530755.5	TSL:2	n.221+31396T>C		intron	N/A
	PARVA	ENST00000533345.5	TSL:5	n.113+10826T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16459 AN: 152162 Hom.: 1069 Cov.: 33

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0659

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0298

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.108 AC: 16455 AN: 152280 Hom.: 1067 Cov.: 33 AF XY: 0.106 AC XY: 7919 AN XY: 74462

African (AFR) AF: 0.0569 AC: 2366 AN: 41546

American (AMR) AF: 0.0658 AC: 1006 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.0301 AC: 156 AN: 5190

South Asian (SAS) AF: 0.186 AC: 900 AN: 4828

European-Finnish (FIN) AF: 0.105 AC: 1113 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10062 AN: 68014

Other (OTH) AF: 0.102 AC: 215 AN: 2116

Alfa AF: 0.127 Hom.: 2984

Bravo AF: 0.0989

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.74
PhyloP100		-0.39
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: rs1426588; hg19: chr11-12430726;