rs2421491

Positions:

• chr1-170724773-T-C

Variant summary

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

The ENST00000239461.11(PRRX1):​c.418-1447T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,182 control chromosomes in the GnomAD database, including 4,392 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 0.21 (4392 hom., cov: 32)
• Consequence: PRRX1 ENST00000239461.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

Genes affected

PRRX1 (HGNC:9142): (paired related homeobox 1) The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins localized to the nucleus. The protein functions as a transcription co-activator, enhancing the DNA-binding activity of serum response factor, a protein required for the induction of genes by growth and differentiation factors. The protein regulates muscle creatine kinase, indicating a role in the establishment of diverse mesodermal muscle types. Alternative splicing yields two isoforms that differ in abundance and expression patterns. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRX1	NM_022716.4	c.418-1447T>C		intron_variant		ENST00000239461.11	NP_073207.1
PRRX1	NM_006902.5	c.418-1447T>C		intron_variant			NP_008833.1
PRRX1	XM_006711388.4	c.277-1447T>C		intron_variant			XP_006711451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRX1	ENST00000239461.11	c.418-1447T>C		intron_variant		1	NM_022716.4	ENSP00000239461	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32566 AN: 152064 Hom.: 4389 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.214 AC: 32576 AN: 152182 Hom.: 4392 Cov.: 32 AF XY: 0.220 AC XY: 16331 AN XY: 74400

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.253

Alfa AF: 0.231 Hom.: 588

Bravo AF: 0.210

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98
DANN	Benign	0.20

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: rs2421491; hg19: chr1-170693914;