rs57609901

Positions:

• chr14-70011466-C-A

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.858-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,561,566 control chromosomes in the GnomAD database, including 35,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2679 hom., cov: 30)
  • Exomes 𝑓: 0.20 (32564 hom.)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.735

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=-0.8).
• BP6: Variant 14-70011466-C-A is Benign according to our data. Variant chr14-70011466-C-A is described in ClinVar as [Benign]. Clinvar id is 257190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.858-19C>A		intron_variant		ENST00000361956.8
SMOC1	NM_022137.6	c.858-19C>A		intron_variant
SMOC1	XM_005267995.2	c.891-19C>A		intron_variant
SMOC1	XM_005267996.2	c.891-19C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.858-19C>A		intron_variant		1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.858-19C>A		intron_variant		1		P4
SMOC1	ENST00000557483.1	n.436-19C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24138 AN: 150564 Hom.: 2672 Cov.: 30

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.211 AC: 52951 AN: 251110 Hom.: 6666 AF XY: 0.208 AC XY: 28197 AN XY: 135728

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.411

Gnomad SAS exome AF: 0.201

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.200 AC: 282363 AN: 1410884 Hom.: 32564 Cov.: 28 AF XY: 0.200 AC XY: 140833 AN XY: 704368

Gnomad4 AFR exome AF: 0.0349

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.160 AC: 24148 AN: 150682 Hom.: 2679 Cov.: 30 AF XY: 0.166 AC XY: 12198 AN XY: 73484

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.174

Alfa AF: 0.169 Hom.: 452

Bravo AF: 0.162

Asia WGS AF: 0.254 AC: 880 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Microphthalmia with limb anomalies Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.46
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs57609901; hg19: chr14-70478183; COSMIC: COSV62759403;