rs227438

chr14-69985897-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.527-6520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,056 control chromosomes in the GnomAD database, including 29,905 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 0.62 (29905 hom., cov: 32)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.527-6520C>T		intron_variant		ENST00000361956.8
SMOC1	NM_022137.6	c.527-6520C>T		intron_variant
SMOC1	XM_005267995.2	c.527-6487C>T		intron_variant
SMOC1	XM_005267996.2	c.527-6487C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.527-6520C>T		intron_variant		1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.527-6520C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94055 AN: 151938 Hom.: 29866 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.619 AC: 94154 AN: 152056 Hom.: 29905 Cov.: 32 AF XY: 0.616 AC XY: 45800 AN XY: 74332

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.630

Alfa AF: 0.618 Hom.: 3658

Bravo AF: 0.621

Asia WGS AF: 0.389 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.2
Dann	Benign	0.48

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: rs227438; hg19: chr14-70452614;