4-1192706-G-C

Position:

• chr4-1192706-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199021.2(SPON2):​c.-238-13165C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,092 control chromosomes in the GnomAD database, including 11,279 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 0.36 (11279 hom., cov: 33)
• Consequence: SPON2 NM_001199021.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

Genes affected

LOC124900647 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124900647	XM_047416477.1	c.-880G>C		5_prime_UTR_variant	2/3		XP_047272433.1
LOC124900647	XM_047416478.1	c.-880G>C		5_prime_UTR_variant	1/5		XP_047272434.1
SPON2	NM_001199021.2	c.-238-13165C>G		intron_variant			NP_001185950.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPON2	ENST00000617421.4	c.-238-13165C>G		intron_variant		5		ENSP00000483599.1
SPON2	ENST00000515004.5	c.-234+2284C>G		intron_variant		4		ENSP00000425871.1
SPON2	ENST00000502483.5	c.-239+2284C>G		intron_variant		4		ENSP00000422516.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54794 AN: 151974 Hom.: 11281 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.360 AC: 54795 AN: 152092 Hom.: 11279 Cov.: 33 AF XY: 0.361 AC XY: 26820 AN XY: 74360

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.335

Alfa AF: 0.296 Hom.: 902

Bravo AF: 0.334

Asia WGS AF: 0.245 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.40

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: rs11247978; hg19: chr4-1186494; COSMIC: COSV72202179; COSMIC: COSV72202179;