rs11565

Positions:

• chr11-14267107-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_006108.4(SPON1):​c.*1420G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0099 in 152,232 control chromosomes in the GnomAD database, including 34 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 0.0099 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPON1 NM_006108.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

Genes affected

SPON1 (HGNC:11252): (spondin 1) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in cell adhesion. Predicted to act upstream of or within positive regulation of protein binding activity; positive regulation of protein processing; and regulation of amyloid precursor protein catabolic process. Located in extracellular space. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

SPON1-AS1 (HGNC:53117): (SPON1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0099 (1507/152232) while in subpopulation AMR AF= 0.0437 (669/15294). AF 95% confidence interval is 0.041. There are 34 homozygotes in gnomad4. There are 756 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPON1	NM_006108.4	c.*1420G>A		3_prime_UTR_variant	16/16	ENST00000576479.4	NP_006099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPON1	ENST00000576479.4	c.*1420G>A		3_prime_UTR_variant	16/16	1	NM_006108.4	ENSP00000460236	P1
SPON1-AS1	ENST00000534587.1	n.39-4060C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00987 AC: 1502 AN: 152114 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00604

Gnomad OTH AF: 0.0143

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00990 AC: 1507 AN: 152232 Hom.: 34 Cov.: 32 AF XY: 0.0102 AC XY: 756 AN XY: 74426

Gnomad4 AFR AF: 0.00209

Gnomad4 AMR AF: 0.0437

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.00831

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00603

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00649 Hom.: 1

Bravo AF: 0.0137

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
DANN	Benign	0.84

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: rs11565; hg19: chr11-14288653;