rs1490512

Positions:

• chr4-118950486-A-T

Variant summary

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

The NM_133477.3(SYNPO2):​c.105+61345A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,152 control chromosomes in the GnomAD database, including 3,458 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 0.19 (3458 hom., cov: 32)
• Consequence: SYNPO2 NM_133477.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

Genes affected

SYNPO2 (HGNC:17732): (synaptopodin 2) Enables alpha-actinin binding activity and filamin binding activity. Involved in positive regulation of actin filament bundle assembly; positive regulation of cell migration; and regulation of Rho-dependent protein serine/threonine kinase activity. Located in several cellular components, including Z disc; focal adhesion; and stress fiber. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNPO2	NM_133477.3	c.105+61345A>T		intron_variant		ENST00000307142.9	NP_597734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNPO2	ENST00000307142.9	c.105+61345A>T		intron_variant		1	NM_133477.3	ENSP00000306015	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29532 AN: 152032 Hom.: 3448 Cov.: 32

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.194 AC: 29556 AN: 152152 Hom.: 3458 Cov.: 32 AF XY: 0.199 AC XY: 14765 AN XY: 74368

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.210

Alfa AF: 0.214 Hom.: 480

Bravo AF: 0.189

Asia WGS AF: 0.254 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.53

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: rs1490512; hg19: chr4-119871641;