1-109473756-A-G

Position:

• chr1-109473756-A-G

Variant summary

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

The NM_001040709.2(SYPL2):​c.130-1825A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,854 control chromosomes in the GnomAD database, including 35,413 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 0.68 (35413 hom., cov: 30)
• Consequence: SYPL2 NM_001040709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.92

Genes affected

SYPL2 (HGNC:27638): (synaptophysin like 2) Involved in substantia nigra development. Predicted to be integral component of membrane. Predicted to be active in synaptic vesicle membrane. [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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYPL2	NM_001040709.2	c.130-1825A>G		intron_variant		ENST00000369872.4	NP_001035799.1
SYPL2	XM_011541283.3	c.130-1825A>G		intron_variant			XP_011539585.1
SYPL2	XM_011541284.3	c.130-1825A>G		intron_variant			XP_011539586.1
SYPL2	XM_011541285.2	c.130-1825A>G		intron_variant			XP_011539587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYPL2	ENST00000369872.4	c.130-1825A>G		intron_variant		1	NM_001040709.2	ENSP00000358888	P1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102507 AN: 151736 Hom.: 35388 Cov.: 30

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.676 AC: 102581 AN: 151854 Hom.: 35413 Cov.: 30 AF XY: 0.678 AC XY: 50285 AN XY: 74198

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.720

Alfa AF: 0.573 Hom.: 1761

Bravo AF: 0.684

Asia WGS AF: 0.806 AC: 2800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.13
DANN	Benign	0.21

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: rs2359653; hg19: chr1-110016378;