chr4-1170520-C-T

Variant names:

• chr4-1170520-C-T
• rs7689089
• NM_012445.4:c.693G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_012445.4(SPON2):​c.693G>A​(p.Lys231Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,613,930 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (67 hom., cov: 34)
  • Exomes 𝑓: 0.0015 (68 hom.)
• Consequence: SPON2 NM_012445.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 4-1170520-C-T is Benign according to our data. Variant chr4-1170520-C-T is described in ClinVar as Benign. ClinVar VariationId is 787269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012445.4. 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
	SPON2	NM_012445.4	MANE Select	c.693G>A	p.Lys231Lys	synonymous	Exon 5 of 6	NP_036577.2	Q9BUD6
	SPON2	NM_001128325.3		c.693G>A	p.Lys231Lys	synonymous	Exon 6 of 7	NP_001121797.2	Q9BUD6
	SPON2	NM_001199021.2		c.693G>A	p.Lys231Lys	synonymous	Exon 7 of 8	NP_001185950.2	Q9BUD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPON2	ENST00000290902.10	TSL:1 MANE Select	c.693G>A	p.Lys231Lys	synonymous	Exon 5 of 6	ENSP00000290902.5	Q9BUD6
	SPON2	ENST00000960395.1		c.1017G>A	p.Lys339Lys	synonymous	Exon 5 of 6	ENSP00000630454.1
	SPON2	ENST00000431380.5	TSL:5	c.693G>A	p.Lys231Lys	synonymous	Exon 6 of 7	ENSP00000394832.1	Q9BUD6

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2254 AN: 152164 Hom.: 68 Cov.: 34

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00363 AC: 909 AN: 250542 AF XY: 0.00262

Gnomad AFR exome AF: 0.0492

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000884

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00155 AC: 2259 AN: 1461648 Hom.: 68 Cov.: 39 AF XY: 0.00131 AC XY: 952 AN XY: 727112

African (AFR) AF: 0.0547 AC: 1831 AN: 33478

American (AMR) AF: 0.00302 AC: 135 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111882

Other (OTH) AF: 0.00338 AC: 204 AN: 60372

GnomAD4 genome AF: 0.0148 AC: 2261 AN: 152282 Hom.: 67 Cov.: 34 AF XY: 0.0148 AC XY: 1102 AN XY: 74458

African (AFR) AF: 0.0513 AC: 2133 AN: 41552

American (AMR) AF: 0.00621 AC: 95 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68016

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00545 Hom.: 7

Bravo AF: 0.0168

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		1.3
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7689089; hg19: chr4-1164308;