chr19-35527424-A-G

Position:

• chr19-35527424-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001166034.2(SBSN):​c.858T>C​(p.Ala286=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 94,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SBSN NM_001166034.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.15

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-35527424-A-G is Benign according to our data. Variant chr19-35527424-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2649720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.15 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBSN	NM_001166034.2	c.858T>C	p.Ala286=	synonymous_variant	1/4	ENST00000452271.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBSN	ENST00000452271.7	c.858T>C	p.Ala286=	synonymous_variant	1/4	1	NM_001166034.2	P2
SBSN	ENST00000518157.1	c.375+483T>C		intron_variant		1		A2
SBSN	ENST00000588674.5	c.315+483T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000560 AC: 53 AN: 94626 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000483

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.000218

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000185

Gnomad OTH AF: 0.000772

GnomAD3 exomes AF: 0.0000384 AC: 8 AN: 208116 Hom.: 0 AF XY: 0.0000522 AC XY: 6 AN XY: 114928

Gnomad AFR exome AF: 0.000321

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000274

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000196 AC: 26 AN: 1323366 Hom.: 0 Cov.: 40 AF XY: 0.0000258 AC XY: 17 AN XY: 658240

Gnomad4 AFR exome AF: 0.000174

Gnomad4 AMR exome AF: 0.000155

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000111

Gnomad4 SAS exome AF: 0.0000359

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000772

Gnomad4 OTH exome AF: 0.0000193

GnomAD4 genome AF: 0.000570 AC: 54 AN: 94672 Hom.: 0 Cov.: 27 AF XY: 0.000616 AC XY: 28 AN XY: 45438

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.000483

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000218

Gnomad4 NFE AF: 0.000185

Gnomad4 OTH AF: 0.000766

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

SBSN: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0030
DANN	Benign	0.12

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: rs77512068; hg19: chr19-36018326;