ENST00000555917.1:n.404+15048T>A

Variant names:

• chr14-69879262-T-A
• rs140427315
• ENST00000555917.1:n.404+15048T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000555917.1(SMOC1):​n.404+15048T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 151,814 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.015 (37 hom., cov: 32)
• Consequence: SMOC1 ENST00000555917.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94
• Publications: 0 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, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 14-69879262-T-A is Benign according to our data. Variant chr14-69879262-T-A is described in ClinVar as Benign. ClinVar VariationId is 1279971.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0149 (2263/151814) while in subpopulation NFE AF = 0.0198 (1345/67892). AF 95% confidence interval is 0.0189. There are 37 homozygotes in GnomAd4. There are 1245 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000555917.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	NM_001034852.3	MANE Select	c.-417T>A		upstream_gene	N/A	NP_001030024.1	Q9H4F8-2
	SMOC1	NM_001425244.1		c.-417T>A		upstream_gene	N/A	NP_001412173.1
	SMOC1	NM_001425245.1		c.-417T>A		upstream_gene	N/A	NP_001412174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000555917.1	TSL:4	n.404+15048T>A		intron	N/A
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.-417T>A		upstream_gene	N/A	ENSP00000355110.4	Q9H4F8-2
	SMOC1	ENST00000381280.4	TSL:1	c.-417T>A		upstream_gene	N/A	ENSP00000370680.4	Q9H4F8-1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 151696 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00320

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.00478

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0149 AC: 2263 AN: 151814 Hom.: 37 Cov.: 32 AF XY: 0.0168 AC XY: 1245 AN XY: 74194

African (AFR) AF: 0.00319 AC: 132 AN: 41384

American (AMR) AF: 0.00681 AC: 104 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5122

South Asian (SAS) AF: 0.00520 AC: 25 AN: 4806

European-Finnish (FIN) AF: 0.0592 AC: 625 AN: 10554

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0198 AC: 1345 AN: 67892

Other (OTH) AF: 0.0119 AC: 25 AN: 2098

Alfa AF: 0.0213 Hom.: 8

Bravo AF: 0.00948

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.70
DANN	Benign	0.76
PhyloP100		-1.9
PromoterAI		0.013	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs140427315; hg19: chr14-70345979;