rs10162517

chr14-69877067-T-C

Variant summary

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

The ENST00000555917.1(SMOC1):n.404+12853T>C 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 0.31 in 152,040 control chromosomes in the GnomAD database, including 7,497 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 0.31 (7497 hom., cov: 32)
• Consequence: SMOC1 ENST00000555917.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 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.404+12853T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47133 AN: 151922 Hom.: 7488 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.310 AC: 47179 AN: 152040 Hom.: 7497 Cov.: 32 AF XY: 0.311 AC XY: 23097 AN XY: 74330

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.295

Alfa AF: 0.314 Hom.: 1143

Bravo AF: 0.298

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.15
Dann	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10162517; hg19: chr14-70343784;