chr14-69985897-C-T

Variant names:

• chr14-69985897-C-T
• rs227438
• NM_001034852.3:c.527-6520C>T

Variant summary

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

The NM_001425244.1(SMOC1):​c.527-6487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,056 control chromosomes in the GnomAD database, including 29,905 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 0.62 (29905 hom., cov: 32)
• Consequence: SMOC1 NM_001425244.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001425244.1. 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.527-6520C>T		intron	N/A	NP_001030024.1
	SMOC1	NM_001425244.1		c.527-6487C>T		intron	N/A	NP_001412173.1
	SMOC1	NM_001425245.1		c.527-6487C>T		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.527-6520C>T		intron	N/A	ENSP00000355110.4
	SMOC1	ENST00000381280.4	TSL:1	c.527-6520C>T		intron	N/A	ENSP00000370680.4
	SMOC1	ENST00000853906.1		c.527-6520C>T		intron	N/A	ENSP00000523965.1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94055 AN: 151938 Hom.: 29866 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.619 AC: 94154 AN: 152056 Hom.: 29905 Cov.: 32 AF XY: 0.616 AC XY: 45800 AN XY: 74332

African (AFR) AF: 0.739 AC: 30675 AN: 41500

American (AMR) AF: 0.599 AC: 9145 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2043 AN: 3466

East Asian (EAS) AF: 0.443 AC: 2298 AN: 5184

South Asian (SAS) AF: 0.351 AC: 1683 AN: 4798

European-Finnish (FIN) AF: 0.652 AC: 6894 AN: 10572

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39523 AN: 67952

Other (OTH) AF: 0.630 AC: 1327 AN: 2108

Alfa AF: 0.618 Hom.: 3658

Bravo AF: 0.621

Asia WGS AF: 0.389 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-0.34
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: rs227438; hg19: chr14-70452614;