rs1472066

Variant names:

• chr4-118942321-A-G
• rs1472066
• NM_133477.3:c.105+53180A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133477.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2	NM_133477.3	MANE Select	c.105+53180A>G		intron	N/A	NP_597734.2	Q9UMS6-2
	SYNPO2	NM_001286754.2		c.13-81109A>G		intron	N/A	NP_001273683.1	Q9UMS6-4
	SYNPO2	NM_001128934.3		c.105+53180A>G		intron	N/A	NP_001122406.1	Q9UMS6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2	ENST00000307142.9	TSL:1 MANE Select	c.105+53180A>G		intron	N/A	ENSP00000306015.4	Q9UMS6-2
	SYNPO2	ENST00000610556.4	TSL:1	c.13-81109A>G		intron	N/A	ENSP00000484885.1	Q9UMS6-4
	SYNPO2	ENST00000434046.6	TSL:1	c.105+53180A>G		intron	N/A	ENSP00000390965.2	Q9UMS6-3

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

African (AFR) AF: 0.0740 AC: 3072 AN: 41530

American (AMR) AF: 0.110 AC: 1676 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.151 AC: 782 AN: 5172

South Asian (SAS) AF: 0.146 AC: 706 AN: 4822

European-Finnish (FIN) AF: 0.148 AC: 1572 AN: 10606

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7755 AN: 68004

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.112 Hom.: 820

Bravo AF: 0.101

Asia WGS AF: 0.157 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.79
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: rs1472066; hg19: chr4-119863476;