8-73081032-G-A

Variant names:

• chr8-73081032-G-A
• rs117453532
• NM_153225.4:c.396C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_153225.4(SBSPON):​c.396C>T​(p.Cys132Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,599,684 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (45 hom.)
• Consequence: SBSPON NM_153225.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.562
• Publications: 2 publications found

Genes affected

SBSPON (HGNC:30362): (somatomedin B and thrombospondin type 1 domain containing) Predicted to be an extracellular matrix structural constituent. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 8-73081032-G-A is Benign according to our data. Variant chr8-73081032-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2658653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.562 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153225.4. 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
	SBSPON	NM_153225.4	MANE Select	c.396C>T	p.Cys132Cys	synonymous	Exon 2 of 5	NP_694957.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBSPON	ENST00000297354.7	TSL:1 MANE Select	c.396C>T	p.Cys132Cys	synonymous	Exon 2 of 5	ENSP00000297354.6	Q8IVN8
	SBSPON	ENST00000964790.1		c.215-9162C>T		intron	N/A	ENSP00000634849.1
	SBSPON	ENST00000519697.1	TSL:2	n.764C>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 865 AN: 152136 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00834

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00555 AC: 1303 AN: 234626 AF XY: 0.00535

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00616

Gnomad ASJ exome AF: 0.00538

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00163

Gnomad NFE exome AF: 0.00900

Gnomad OTH exome AF: 0.00699

GnomAD4 exome AF: 0.00723 AC: 10466 AN: 1447430 Hom.: 45 Cov.: 31 AF XY: 0.00713 AC XY: 5129 AN XY: 719364

African (AFR) AF: 0.00140 AC: 46 AN: 32968

American (AMR) AF: 0.00609 AC: 256 AN: 42034

Ashkenazi Jewish (ASJ) AF: 0.00533 AC: 133 AN: 24962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.000119 AC: 10 AN: 83792

European-Finnish (FIN) AF: 0.00224 AC: 119 AN: 53010

Middle Eastern (MID) AF: 0.00546 AC: 31 AN: 5674

European-Non Finnish (NFE) AF: 0.00858 AC: 9487 AN: 1105712

Other (OTH) AF: 0.00643 AC: 384 AN: 59758

GnomAD4 genome AF: 0.00569 AC: 866 AN: 152254 Hom.: 8 Cov.: 32 AF XY: 0.00521 AC XY: 388 AN XY: 74464

African (AFR) AF: 0.00156 AC: 65 AN: 41536

American (AMR) AF: 0.00993 AC: 152 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00834 AC: 567 AN: 68016

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00725 Hom.: 3

Bravo AF: 0.00576

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		0.56
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs117453532; hg19: chr8-73993267;