14-69899207-A-C

Position:

• chr14-69899207-A-C

Variant summary

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

The NM_001034852.3(SMOC1):​c.99+19430A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,114 control chromosomes in the GnomAD database, including 39,043 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 0.67 (39043 hom., cov: 32)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.99+19430A>C		intron_variant		ENST00000361956.8
SMOC1	NM_022137.6	c.99+19430A>C		intron_variant
SMOC1	XM_005267995.2	c.99+19430A>C		intron_variant
SMOC1	XM_005267996.2	c.99+19430A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.99+19430A>C		intron_variant		1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.99+19430A>C		intron_variant		1		P4
SMOC1	ENST00000555917.1	n.404+34993A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102154 AN: 151996 Hom.: 39037 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.672 AC: 102187 AN: 152114 Hom.: 39043 Cov.: 32 AF XY: 0.679 AC XY: 50467 AN XY: 74364

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.693

Alfa AF: 0.682 Hom.: 3254

Bravo AF: 0.648

Asia WGS AF: 0.786 AC: 2729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
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: rs11627546; hg19: chr14-70365924;