4-1167607-T-C

Position:

• chr4-1167607-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_012445.4(SPON2):​c.861A>G​(p.Gly287Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000645 in 1,613,114 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: SPON2 NM_012445.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.321

Genes affected

SPON2 (HGNC:11253): (spondin 2) Predicted to enable antigen binding activity; lipopolysaccharide binding activity; and metal ion binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within several processes, including defense response to other organism; opsonization; and positive regulation of cytokine production. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LOC124900647 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-1167607-T-C is Benign according to our data. Variant chr4-1167607-T-C is described in ClinVar as [Benign]. Clinvar id is 737377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.321 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPON2	NM_012445.4	c.861A>G	p.Gly287Gly	synonymous_variant	6/6	ENST00000290902.10	NP_036577.2
SPON2	NM_001128325.3	c.861A>G	p.Gly287Gly	synonymous_variant	7/7		NP_001121797.2
SPON2	NM_001199021.2	c.861A>G	p.Gly287Gly	synonymous_variant	8/8		NP_001185950.2
LOC124900647	XM_047416477.1	c.-2486-23493T>C		intron_variant			XP_047272433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPON2	ENST00000290902.10	c.861A>G	p.Gly287Gly	synonymous_variant	6/6	1	NM_012445.4	ENSP00000290902.5
SPON2	ENST00000431380.5	c.861A>G	p.Gly287Gly	synonymous_variant	7/7	5		ENSP00000394832.1
SPON2	ENST00000617421.4	c.861A>G	p.Gly287Gly	synonymous_variant	8/8	5		ENSP00000483599.1

Frequencies

GnomAD3 genomes AF: 0.00340 AC: 517 AN: 152024 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000917 AC: 229 AN: 249746 Hom.: 0 AF XY: 0.000673 AC XY: 91 AN XY: 135120

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.000667

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000936

Gnomad NFE exome AF: 0.0000799

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000359 AC: 524 AN: 1460972 Hom.: 2 Cov.: 30 AF XY: 0.000327 AC XY: 238 AN XY: 726822

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.000917

Gnomad4 ASJ exome AF: 0.000957

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000133

Gnomad4 NFE exome AF: 0.0000477

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.00339 AC: 516 AN: 152142 Hom.: 1 Cov.: 32 AF XY: 0.00328 AC XY: 244 AN XY: 74390

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00150 Hom.: 0

Bravo AF: 0.00384

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148503555; hg19: chr4-1161395;