rs4902759

Variant names:

• chr14-69862236-C-T
• rs4902759
• ENST00000555917.1:n.352-1926C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555917.1(SMOC1):​n.352-1926C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,960 control chromosomes in the GnomAD database, including 17,224 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 0.45 (17224 hom., cov: 31)
• Consequence: SMOC1 ENST00000555917.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000555917.1	n.352-1926C>T		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68149 AN: 151842 Hom.: 17226 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.448 AC: 68153 AN: 151960 Hom.: 17224 Cov.: 31 AF XY: 0.453 AC XY: 33647 AN XY: 74294

African (AFR) AF: 0.201 AC: 8344 AN: 41414

American (AMR) AF: 0.518 AC: 7919 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1912 AN: 3466

East Asian (EAS) AF: 0.780 AC: 4035 AN: 5170

South Asian (SAS) AF: 0.483 AC: 2324 AN: 4814

European-Finnish (FIN) AF: 0.551 AC: 5812 AN: 10540

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36199 AN: 67972

Other (OTH) AF: 0.480 AC: 1006 AN: 2098

Alfa AF: 0.477 Hom.: 2405

Bravo AF: 0.442

Asia WGS AF: 0.616 AC: 2140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.81
PhyloP100		0.0050

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4902759; hg19: chr14-70328953;