19-35526806-C-T

Variant names:

• chr19-35526806-C-T
• rs774392200
• NM_001166034.2:c.1476G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001166034.2(SBSN):​c.1476G>A​(p.Glu492Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SBSN NM_001166034.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 0 publications found

Genes affected

SBSN (HGNC:24950): (suprabasin) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.094 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166034.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBSN	NM_001166034.2	MANE Select	c.1476G>A	p.Glu492Glu	synonymous	Exon 1 of 4	NP_001159506.1	Q6UWP8-1
	SBSN	NM_198538.4		c.447G>A	p.Glu149Glu	synonymous	Exon 2 of 5	NP_940940.1	Q6UWP8-2
	SBSN	NM_001166035.2		c.375+1101G>A		intron	N/A	NP_001159507.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBSN	ENST00000452271.7	TSL:1 MANE Select	c.1476G>A	p.Glu492Glu	synonymous	Exon 1 of 4	ENSP00000430242.1	Q6UWP8-1
	SBSN	ENST00000518157.1	TSL:1	c.447G>A	p.Glu149Glu	synonymous	Exon 2 of 5	ENSP00000428771.1	Q6UWP8-2
	SBSN	ENST00000588674.5	TSL:2	c.315+1101G>A		intron	N/A	ENSP00000468646.2	K7ESC4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.0
DANN	Benign	0.43
PhyloP100		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs774392200; hg19: chr19-36017708;