14-69989982-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001034852.3(SMOC1):c.527-2435T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,100 control chromosomes in the GnomAD database, including 21,125 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 0.52 (21125 hom., cov: 33)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.527-2435T>G		intron_variant		ENST00000361956.8
SMOC1	NM_022137.6	c.527-2435T>G		intron_variant
SMOC1	XM_005267995.2	c.527-2402T>G		intron_variant
SMOC1	XM_005267996.2	c.527-2402T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.527-2435T>G		intron_variant		1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.527-2435T>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79339 AN: 151982 Hom.: 21097 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.522 AC: 79426 AN: 152100 Hom.: 21125 Cov.: 33 AF XY: 0.524 AC XY: 38954 AN XY: 74364

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.519

Alfa AF: 0.485 Hom.: 17194

Bravo AF: 0.520

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	17
Dann	Benign	0.77

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: rs227425; hg19: chr14-70456699;