rs1750043

Positions:

• chr6-158041474-A-G
• chr6-158041474-A-T

Variant summary

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

The NM_003898.4(SYNJ2):​c.712-1842A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,090 control chromosomes in the GnomAD database, including 19,147 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 0.50 (19147 hom., cov: 33)
• Consequence: SYNJ2 NM_003898.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

SYNJ2 (HGNC:11504): (synaptojanin 2) The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

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 (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.712-1842A>G		intron_variant		ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9	c.712-1842A>G		intron_variant		1	NM_003898.4	ENSP00000347792.4
SYNJ2	ENST00000640338.1	c.712-1842A>G		intron_variant		1		ENSP00000492532.1
SYNJ2	ENST00000638626.1	c.1-1842A>G		intron_variant		1		ENSP00000492369.1
SYNJ2	ENST00000485863.1	n.190-1842A>G		intron_variant		3		ENSP00000436657.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75335 AN: 151972 Hom.: 19120 Cov.: 33

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.496 AC: 75404 AN: 152090 Hom.: 19147 Cov.: 33 AF XY: 0.490 AC XY: 36465 AN XY: 74364

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.465

Alfa AF: 0.484 Hom.: 21428

Bravo AF: 0.498

Asia WGS AF: 0.544 AC: 1892 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	0.32
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1750043; hg19: chr6-158462506;