20-45367240-T-G

Variant names:

• chr20-45367240-T-G
• rs2245717
• ENST00000457307.1:n.*494T>G

Variant summary

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

The ENST00000457307.1(SYS1):​n.*494T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,506,226 control chromosomes in the GnomAD database, including 450,965 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 0.79 (47604 hom., cov: 31)
  • Exomes 𝑓: 0.77 (403361 hom.)
• Consequence: SYS1 ENST00000457307.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 25 publications found

Genes affected

SYS1 (HGNC:16162): (SYS1 golgi trafficking protein) SYS1 forms a complex with ADP-ribosylation factor-related protein ARFRP1 (MIM 604699) and targets ARFRP1 to the Golgi apparatus (Behnia et al., 2004 [PubMed 15077113]).[supplied by OMIM, Aug 2009]

SYS1-DBNDD2 (HGNC:33535): (SYS1-DBNDD2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription from the neighboring SYS1 Golgi-localized integral membrane protein homolog and dysbindin domain containing 2 (DBNDD2) genes. The read-through transcript includes the majority of exons from each individual gene, but it would be subject to nonsense-mediated mRNA decay (NMD) and is therefore predicted to be non-coding. [provided by RefSeq, Oct 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457307.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYS1	NM_033542.4	MANE Select	c.*125T>G		3_prime_UTR	Exon 4 of 4	NP_291020.1
	SYS1	NM_001197129.2		c.*125T>G		3_prime_UTR	Exon 5 of 5	NP_001184058.1
	SYS1	NM_001099791.3		c.230+1554T>G		intron	N/A	NP_001093261.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYS1	ENST00000457307.1	TSL:1	n.*494T>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000397601.1
	SYS1	ENST00000243918.10	TSL:1 MANE Select	c.*125T>G		3_prime_UTR	Exon 4 of 4	ENSP00000243918.5
	SYS1	ENST00000457307.1	TSL:1	n.*494T>G		3_prime_UTR	Exon 4 of 4	ENSP00000397601.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119884 AN: 151958 Hom.: 47547 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.770 AC: 1043248 AN: 1354150 Hom.: 403361 Cov.: 47 AF XY: 0.772 AC XY: 511200 AN XY: 662502

African (AFR) AF: 0.856 AC: 26084 AN: 30488

American (AMR) AF: 0.782 AC: 22647 AN: 28970

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 16694 AN: 20062

East Asian (EAS) AF: 0.550 AC: 21135 AN: 38450

South Asian (SAS) AF: 0.800 AC: 55535 AN: 69412

European-Finnish (FIN) AF: 0.747 AC: 33357 AN: 44664

Middle Eastern (MID) AF: 0.814 AC: 3636 AN: 4466

European-Non Finnish (NFE) AF: 0.773 AC: 821105 AN: 1061638

Other (OTH) AF: 0.769 AC: 43055 AN: 56000

GnomAD4 genome AF: 0.789 AC: 119999 AN: 152076 Hom.: 47604 Cov.: 31 AF XY: 0.787 AC XY: 58529 AN XY: 74334

African (AFR) AF: 0.852 AC: 35361 AN: 41520

American (AMR) AF: 0.780 AC: 11912 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2908 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2802 AN: 5134

South Asian (SAS) AF: 0.793 AC: 3825 AN: 4826

European-Finnish (FIN) AF: 0.754 AC: 7965 AN: 10560

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52641 AN: 67974

Other (OTH) AF: 0.788 AC: 1663 AN: 2110

Alfa AF: 0.782 Hom.: 72076

Bravo AF: 0.788

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2245717; hg19: chr20-43995880; COSMIC: COSV54782100; COSMIC: COSV54782100;