chr1-109472561-G-A

Variant names:

• chr1-109472561-G-A
• rs4970767
• NM_001040709.2:c.130-3020G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SYPL2	NM_001040709.2	c.130-3020G>A		intron_variant	Intron 2 of 5	ENST00000369872.4	NP_001035799.1
SYPL2	XM_011541283.3	c.130-3020G>A		intron_variant	Intron 2 of 6		XP_011539585.1
SYPL2	XM_011541284.3	c.130-3020G>A		intron_variant	Intron 2 of 5		XP_011539586.1
SYPL2	XM_011541285.2	c.130-3020G>A		intron_variant	Intron 2 of 4		XP_011539587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYPL2	ENST00000369872.4	c.130-3020G>A		intron_variant	Intron 2 of 5	1	NM_001040709.2	ENSP00000358888.3

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

African (AFR) AF: 0.553 AC: 22193 AN: 40158

American (AMR) AF: 0.788 AC: 11795 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2784 AN: 3468

East Asian (EAS) AF: 0.958 AC: 4903 AN: 5116

South Asian (SAS) AF: 0.728 AC: 3463 AN: 4756

European-Finnish (FIN) AF: 0.668 AC: 6545 AN: 9800

Middle Eastern (MID) AF: 0.714 AC: 207 AN: 290

European-Non Finnish (NFE) AF: 0.697 AC: 47222 AN: 67766

Other (OTH) AF: 0.724 AC: 1505 AN: 2080

Alfa AF: 0.659 Hom.: 4121

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
PhyloP100		-0.95
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: rs4970767; hg19: chr1-110015183;