4-118942321-A-G

Position:

• chr4-118942321-A-G

Variant summary

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

The NM_133477.3(SYNPO2):​c.105+53180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,216 control chromosomes in the GnomAD database, including 946 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 (946 hom., cov: 32)
• Consequence: SYNPO2 NM_133477.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNPO2	NM_133477.3	c.105+53180A>G		intron_variant		ENST00000307142.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNPO2	ENST00000307142.9	c.105+53180A>G		intron_variant		1	NM_133477.3	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16304 AN: 152098 Hom.: 945 Cov.: 32

Gnomad AFR AF: 0.0738

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0990

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

GnomAD4 genome AF: 0.107 AC: 16323 AN: 152216 Hom.: 946 Cov.: 32 AF XY: 0.110 AC XY: 8198 AN XY: 74424

Gnomad4 AFR AF: 0.0740

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.101

Alfa AF: 0.113 Hom.: 566

Bravo AF: 0.101

Asia WGS AF: 0.157 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.69

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: rs1472066; hg19: chr4-119863476;