rs11626232

chr14-70020679-C-T

Variant summary

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

The NM_001034852.3(SMOC1):c.1047-2524C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,114 control chromosomes in the GnomAD database, including 1,011 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 0.11 (1011 hom., cov: 32)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.1047-2524C>T		intron_variant		ENST00000361956.8
SMOC1	NM_022137.6	c.1047-2524C>T		intron_variant
SMOC1	XM_005267995.2	c.1080-2524C>T		intron_variant
SMOC1	XM_005267996.2	c.1080-2524C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.1047-2524C>T		intron_variant		1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.1047-2524C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16328 AN: 151996 Hom.: 1010 Cov.: 32

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.107 AC: 16327 AN: 152114 Hom.: 1011 Cov.: 32 AF XY: 0.102 AC XY: 7584 AN XY: 74368

Gnomad4 AFR AF: 0.0730

Gnomad4 AMR AF: 0.0952

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.124

Alfa AF: 0.118 Hom.: 148

Bravo AF: 0.106

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.052
Dann	Benign	0.31

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: rs11626232; hg19: chr14-70487396;