rs227422

Positions:

• chr14-69990936-A-C
• chr14-69990936-A-T

Variant summary

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

The NM_001034852.3(SMOC1):​c.527-1481A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,474 control chromosomes in the GnomAD database, including 15,974 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 0.44 (15974 hom., cov: 31)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.527-1481A>C		intron_variant		ENST00000361956.8
SMOC1	NM_022137.6	c.527-1481A>C		intron_variant
SMOC1	XM_005267995.2	c.527-1448A>C		intron_variant
SMOC1	XM_005267996.2	c.527-1448A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.527-1481A>C		intron_variant		1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.527-1481A>C		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66637 AN: 151356 Hom.: 15949 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.440 AC: 66718 AN: 151474 Hom.: 15974 Cov.: 31 AF XY: 0.439 AC XY: 32468 AN XY: 74000

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.416

Alfa AF: 0.320 Hom.: 1515

Bravo AF: 0.454

Asia WGS AF: 0.334 AC: 1162 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.82

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: rs227422; hg19: chr14-70457653;