rs227418

Variant names:

• chr14-69992995-C-T
• rs227418
• NM_001034852.3:c.583+522C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

SMOC1 Gene-Disease associations (from GenCC):

• microphthalmia with limb anomalies

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	NM_001034852.3	MANE Select	c.583+522C>T		intron	N/A	NP_001030024.1
	SMOC1	NM_001425244.1		c.616+522C>T		intron	N/A	NP_001412173.1
	SMOC1	NM_001425245.1		c.616+522C>T		intron	N/A	NP_001412174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.583+522C>T		intron	N/A	ENSP00000355110.4
	SMOC1	ENST00000381280.4	TSL:1	c.583+522C>T		intron	N/A	ENSP00000370680.4

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

African (AFR) AF: 0.438 AC: 18155 AN: 41462

American (AMR) AF: 0.125 AC: 1908 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3470

East Asian (EAS) AF: 0.0579 AC: 300 AN: 5184

South Asian (SAS) AF: 0.0363 AC: 175 AN: 4820

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10568

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10777 AN: 67996

Other (OTH) AF: 0.191 AC: 404 AN: 2114

Alfa AF: 0.170 Hom.: 4549

Bravo AF: 0.229

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.82
PhyloP100		0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs227418; hg19: chr14-70459712;