14-69879633-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.-46G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,389,404 control chromosomes in the GnomAD database, including 5,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (323 hom., cov: 33)
  • Exomes 𝑓: 0.083 (4931 hom.)
• Consequence: SMOC1 NM_001034852.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24

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=-0.73).
• BP6: Variant 14-69879633-G-A is Benign according to our data. Variant chr14-69879633-G-A is described in ClinVar as [Benign]. Clinvar id is 1230923.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.-46G>A		5_prime_UTR_variant	1/12	ENST00000361956.8
SMOC1	NM_022137.6	c.-46G>A		5_prime_UTR_variant	1/12
SMOC1	XM_005267995.2	c.-46G>A		5_prime_UTR_variant	1/12
SMOC1	XM_005267996.2	c.-46G>A		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.-46G>A		5_prime_UTR_variant	1/12	1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.-46G>A		5_prime_UTR_variant	1/12	1		P4
SMOC1	ENST00000555917.1	n.404+15419G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8100 AN: 152108 Hom.: 323 Cov.: 33

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0319

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0853

Gnomad OTH AF: 0.0564

GnomAD3 exomes AF: 0.0684 AC: 3063 AN: 44762 Hom.: 156 AF XY: 0.0662 AC XY: 1768 AN XY: 26704

Gnomad AFR exome AF: 0.0198

Gnomad AMR exome AF: 0.0512

Gnomad ASJ exome AF: 0.0772

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0196

Gnomad FIN exome AF: 0.0432

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0784

GnomAD4 exome AF: 0.0835 AC: 103303 AN: 1237186 Hom.: 4931 Cov.: 22 AF XY: 0.0819 AC XY: 49767 AN XY: 607548

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.0492

Gnomad4 ASJ exome AF: 0.0668

Gnomad4 EAS exome AF: 0.0000365

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.0393

Gnomad4 NFE exome AF: 0.0947

Gnomad4 OTH exome AF: 0.0692

GnomAD4 genome AF: 0.0532 AC: 8098 AN: 152218 Hom.: 323 Cov.: 33 AF XY: 0.0495 AC XY: 3688 AN XY: 74432

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0319

Gnomad4 NFE AF: 0.0853

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0645 Hom.: 49

Bravo AF: 0.0537

Asia WGS AF: 0.0100 AC: 35 AN: 3466

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 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	14
Dann	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs146095118; hg19: chr14-70346350;