19-35525296-A-G

Variant names:

• chr19-35525296-A-G
• rs2285513
• NM_001166034.2:c.1639-372T>C

Variant summary

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

The NM_001166034.2(SBSN):​c.1639-372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,718 control chromosomes in the GnomAD database, including 25,099 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 0.57 (25099 hom., cov: 30)
• Consequence: SBSN NM_001166034.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 7 publications found

Genes affected

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

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 (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

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.1639-372T>C		intron	N/A	NP_001159506.1	Q6UWP8-1
	SBSN	NM_198538.4		c.610-372T>C		intron	N/A	NP_940940.1	Q6UWP8-2
	SBSN	NM_001166035.2		c.376-372T>C		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.1639-372T>C		intron	N/A	ENSP00000430242.1	Q6UWP8-1
	SBSN	ENST00000518157.1	TSL:1	c.610-372T>C		intron	N/A	ENSP00000428771.1	Q6UWP8-2
	SBSN	ENST00000588674.5	TSL:2	c.316-372T>C		intron	N/A	ENSP00000468646.2	K7ESC4

Frequencies

GnomAD3 genomes AF: 0.574 AC: 86980 AN: 151598 Hom.: 25060 Cov.: 30

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.574 AC: 87077 AN: 151718 Hom.: 25099 Cov.: 30 AF XY: 0.576 AC XY: 42726 AN XY: 74116

African (AFR) AF: 0.612 AC: 25271 AN: 41318

American (AMR) AF: 0.588 AC: 8966 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1659 AN: 3468

East Asian (EAS) AF: 0.565 AC: 2897 AN: 5128

South Asian (SAS) AF: 0.612 AC: 2944 AN: 4812

European-Finnish (FIN) AF: 0.607 AC: 6403 AN: 10550

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37252 AN: 67886

Other (OTH) AF: 0.525 AC: 1107 AN: 2108

Alfa AF: 0.552 Hom.: 97396

Bravo AF: 0.574

Asia WGS AF: 0.575 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.089
DANN	Benign	0.64
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2285513;

hg19: chr19-36016198;