rs1885482

Positions:

• chr14-70013498-T-A
• chr14-70013498-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001034852.3(SMOC1):​c.1046+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,612,844 control chromosomes in the GnomAD database, including 23,863 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3509 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20354 hom.)
• Consequence: SMOC1 NM_001034852.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006533
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.137

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 14-70013498-T-A is Benign according to our data. Variant chr14-70013498-T-A is described in ClinVar as [Benign]. Clinvar id is 257186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.1046+7T>A		splice_region_variant, intron_variant		ENST00000361956.8
SMOC1	NM_022137.6	c.1046+7T>A		splice_region_variant, intron_variant
SMOC1	XM_005267995.2	c.1079+7T>A		splice_region_variant, intron_variant
SMOC1	XM_005267996.2	c.1079+7T>A		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.1046+7T>A		splice_region_variant, intron_variant		1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.1046+7T>A		splice_region_variant, intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30567 AN: 151814 Hom.: 3511 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.153 AC: 38477 AN: 251140 Hom.: 3586 AF XY: 0.146 AC XY: 19801 AN XY: 135736

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.00881

Gnomad SAS exome AF: 0.0499

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.160 AC: 233640 AN: 1460912 Hom.: 20354 Cov.: 31 AF XY: 0.156 AC XY: 113388 AN XY: 726832

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0233

Gnomad4 SAS exome AF: 0.0503

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.201 AC: 30591 AN: 151932 Hom.: 3509 Cov.: 32 AF XY: 0.198 AC XY: 14678 AN XY: 74262

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.192

Alfa AF: 0.130 Hom.: 481

Bravo AF: 0.205

Asia WGS AF: 0.0650 AC: 229 AN: 3478

EpiCase AF: 0.161

EpiControl AF: 0.157

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1885482; hg19: chr14-70480215; COSMIC: COSV62764027; COSMIC: COSV62764027;