14-69880631-A-G

Variant names:

• chr14-69880631-A-G
• rs11158820
• NM_001034852.3:c.99+854A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001034852.3(SMOC1):​c.99+854A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,086 control chromosomes in the GnomAD database, including 28,813 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 0.58 (28813 hom., cov: 32)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39
• Publications: 15 publications found

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]

SMOC1 Gene-Disease associations (from GenCC):

• microphthalmia with limb anomalies

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	NM_001034852.3	MANE Select	c.99+854A>G		intron	N/A	NP_001030024.1
	SMOC1	NM_001425244.1		c.99+854A>G		intron	N/A	NP_001412173.1
	SMOC1	NM_001425245.1		c.99+854A>G		intron	N/A	NP_001412174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.99+854A>G		intron	N/A	ENSP00000355110.4
	SMOC1	ENST00000381280.4	TSL:1	c.99+854A>G		intron	N/A	ENSP00000370680.4
	SMOC1	ENST00000555917.1	TSL:4	n.404+16417A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88020 AN: 151968 Hom.: 28810 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.579 AC: 88040 AN: 152086 Hom.: 28813 Cov.: 32 AF XY: 0.587 AC XY: 43630 AN XY: 74340

African (AFR) AF: 0.256 AC: 10620 AN: 41444

American (AMR) AF: 0.713 AC: 10904 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3470

East Asian (EAS) AF: 0.955 AC: 4953 AN: 5184

South Asian (SAS) AF: 0.624 AC: 3004 AN: 4812

European-Finnish (FIN) AF: 0.722 AC: 7643 AN: 10586

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46648 AN: 67998

Other (OTH) AF: 0.617 AC: 1296 AN: 2102

Alfa AF: 0.646 Hom.: 93543

Bravo AF: 0.566

Asia WGS AF: 0.748 AC: 2601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.58
PhyloP100		3.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11158820; hg19: chr14-70347348;