14-69952081-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001034852.3(SMOC1):c.100-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,583,550 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (147 hom., cov: 32)
  • Exomes 𝑓: 0.014 (305 hom.)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.461

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-69952081-G-A is Benign according to our data. Variant chr14-69952081-G-A is described in ClinVar as [Benign]. Clinvar id is 1222405.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.100-57G>A		intron_variant		ENST00000361956.8
SMOC1	NM_022137.6	c.100-57G>A		intron_variant
SMOC1	XM_005267995.2	c.100-57G>A		intron_variant
SMOC1	XM_005267996.2	c.100-57G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.100-57G>A		intron_variant		1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.100-57G>A		intron_variant		1		P4
SMOC1	ENST00000555917.1	n.405-57G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4940 AN: 152042 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0141 AC: 20202 AN: 1431390 Hom.: 305 AF XY: 0.0140 AC XY: 9977 AN XY: 713946

Gnomad4 AFR exome AF: 0.0837

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.0249

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00708

Gnomad4 FIN exome AF: 0.00315

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.0207

GnomAD4 genome AF: 0.0325 AC: 4941 AN: 152160 Hom.: 147 Cov.: 32 AF XY: 0.0307 AC XY: 2283 AN XY: 74388

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0222 Hom.: 22

Bravo AF: 0.0367

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.13
Dann	Benign	0.72

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: rs28367033; hg19: chr14-70418798;