rs11611541

Variant names:

• chr12-120262686-C-T
• rs11611541
• NM_001385981.1:c.13+2931G>A

Variant summary

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

The NM_001385981.1(PXN):​c.13+2931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,186 control chromosomes in the GnomAD database, including 1,650 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 0.14 (1650 hom., cov: 32)
• Consequence: PXN NM_001385981.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 6 publications found

Genes affected

PXN (HGNC:9718): (paxillin) This gene encodes a cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. These isoforms exhibit different expression pattern, and have different biochemical, as well as physiological properties (PMID:9054445). [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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXN	NM_001385981.1	c.13+2931G>A		intron_variant	Intron 1 of 14	ENST00000637617.2	NP_001372910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXN	ENST00000637617.2	c.13+2931G>A		intron_variant	Intron 1 of 14	5	NM_001385981.1	ENSP00000489840.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21286 AN: 152068 Hom.: 1652 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.140 AC: 21289 AN: 152186 Hom.: 1650 Cov.: 32 AF XY: 0.141 AC XY: 10490 AN XY: 74390

African (AFR) AF: 0.126 AC: 5225 AN: 41520

American (AMR) AF: 0.112 AC: 1711 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0714 AC: 345 AN: 4832

European-Finnish (FIN) AF: 0.200 AC: 2118 AN: 10570

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10743 AN: 68004

Other (OTH) AF: 0.132 AC: 280 AN: 2114

Alfa AF: 0.148 Hom.: 2229

Bravo AF: 0.133

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.14
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: rs11611541; hg19: chr12-120700489;