rs227418

Positions:

• chr14-69992995-C-T

Variant summary

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

The NM_001034852.3(SMOC1):​c.583+522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,106 control chromosomes in the GnomAD database, including 5,406 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 0.23 (5406 hom., cov: 32)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

Genes affected

SMOC1 (HGNC:20318): (SPARC related modular calcium binding 1) This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMOC1	NM_001034852.3	c.583+522C>T		intron_variant		ENST00000361956.8	NP_001030024.1
SMOC1	NM_022137.6	c.583+522C>T		intron_variant			NP_071420.1
SMOC1	XM_005267995.2	c.616+522C>T		intron_variant			XP_005268052.1
SMOC1	XM_005267996.2	c.616+522C>T		intron_variant			XP_005268053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8	c.583+522C>T		intron_variant		1	NM_001034852.3	ENSP00000355110	A2
SMOC1	ENST00000381280.4	c.583+522C>T		intron_variant		1		ENSP00000370680	P4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34738 AN: 151990 Hom.: 5398 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.229 AC: 34780 AN: 152106 Hom.: 5406 Cov.: 32 AF XY: 0.224 AC XY: 16662 AN XY: 74340

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.0579

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.191

Alfa AF: 0.161 Hom.: 2745

Bravo AF: 0.229

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.82

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: rs227418; hg19: chr14-70459712;