rs350294

Variant names:

• chr6-158099285-C-T
• rs350294
• ENST00000822161.1:n.56+37C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000822161.1(ENSG00000306953):​n.56+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,850 control chromosomes in the GnomAD database, including 38,213 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 0.70 (38201 hom., cov: 30)
  • Exomes 𝑓: 0.61 (12 hom.)
• Consequence: ENSG00000306953 ENST00000822161.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 2 publications found

Genes affected

ENSG00000306953 (HGNC:):

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4	c.*2921C>T		downstream_gene_variant		ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000306953	ENST00000822161.1	n.56+37C>T		intron_variant	Intron 1 of 1
SYNJ2	ENST00000355585.9	c.*2921C>T		downstream_gene_variant		1	NM_003898.4	ENSP00000347792.4
SYNJ2	ENST00000638626.1	c.*2921C>T		downstream_gene_variant		1		ENSP00000492369.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105592 AN: 151666 Hom.: 38161 Cov.: 30

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.663

GnomAD4 exome AF: 0.606 AC: 40 AN: 66 Hom.: 12 AF XY: 0.583 AC XY: 28 AN XY: 48

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.586 AC: 34 AN: 58

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.696 AC: 105671 AN: 151784 Hom.: 38201 Cov.: 30 AF XY: 0.691 AC XY: 51235 AN XY: 74178

African (AFR) AF: 0.896 AC: 37150 AN: 41442

American (AMR) AF: 0.483 AC: 7367 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2130 AN: 3464

East Asian (EAS) AF: 0.585 AC: 3028 AN: 5172

South Asian (SAS) AF: 0.684 AC: 3287 AN: 4806

European-Finnish (FIN) AF: 0.632 AC: 6609 AN: 10454

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43832 AN: 67886

Other (OTH) AF: 0.661 AC: 1395 AN: 2110

Alfa AF: 0.674 Hom.: 4430

Bravo AF: 0.691

Asia WGS AF: 0.656 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.69
DANN	Benign	0.77
PhyloP100		-0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs350294; hg19: chr6-158520317;