rs4902759

chr14-69862236-C-T

Variant summary

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

The ENST00000555917.1(SMOC1):n.352-1926C>T variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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=-0.9).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000555917.1	n.352-1926C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.480

Alfa AF: 0.487 Hom.: 2381

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4902759; hg19: chr14-70328953;