chr14-69880631-A-G

Position:

• chr14-69880631-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMOC1	NM_001034852.3	c.99+854A>G		intron_variant		ENST00000361956.8	NP_001030024.1
SMOC1	NM_022137.6	c.99+854A>G		intron_variant			NP_071420.1
SMOC1	XM_005267995.2	c.99+854A>G		intron_variant
SMOC1	XM_005267996.2	c.99+854A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8	c.99+854A>G		intron_variant		1	NM_001034852.3	ENSP00000355110.4
SMOC1	ENST00000381280.4	c.99+854A>G		intron_variant		1		ENSP00000370680.4
SMOC1	ENST00000555917.1	n.404+16417A>G		intron_variant		4

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

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.617

Alfa AF: 0.665 Hom.: 34652

Bravo AF: 0.566

Asia WGS AF: 0.748 AC: 2601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.58

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: rs11158820; hg19: chr14-70347348;