rs4970767

Positions:

• chr1-109472561-G-A
• chr1-109472561-G-T

Variant summary

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

The NM_001040709.2(SYPL2):​c.130-3020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 149,304 control chromosomes in the GnomAD database, including 34,990 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 (34990 hom., cov: 25)
• Consequence: SYPL2 NM_001040709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950

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=-0.92).
• 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	UniProt
SYPL2	NM_001040709.2	c.130-3020G>A		intron_variant		ENST00000369872.4
SYPL2	XM_011541283.3	c.130-3020G>A		intron_variant
SYPL2	XM_011541284.3	c.130-3020G>A		intron_variant
SYPL2	XM_011541285.2	c.130-3020G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYPL2	ENST00000369872.4	c.130-3020G>A		intron_variant		1	NM_001040709.2	P1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 101168 AN: 149190 Hom.: 34965 Cov.: 25

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.678 AC: 101241 AN: 149304 Hom.: 34990 Cov.: 25 AF XY: 0.680 AC XY: 49410 AN XY: 72648

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.724

Alfa AF: 0.663 Hom.: 3999

Bravo AF: 0.685

Asia WGS AF: 0.806 AC: 2802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.076
DANN	Benign	0.36

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: rs4970767; hg19: chr1-110015183;