rs1885482

Variant names:

• chr14-70013498-T-A
• rs1885482
• NM_001034852.3:c.1046+7T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-70013498-T-A
• chr14-70013498-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001034852.3(SMOC1):​c.1046+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,612,844 control chromosomes in the GnomAD database, including 23,863 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3509 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20354 hom.)
• Consequence: SMOC1 NM_001034852.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006533
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.137
• Publications: 7 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 14-70013498-T-A is Benign according to our data. Variant chr14-70013498-T-A is described in ClinVar as Benign. ClinVar VariationId is 257186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034852.3. 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.1046+7T>A		splice_region intron	N/A	NP_001030024.1	Q9H4F8-2
	SMOC1	NM_001425244.1		c.1079+7T>A		splice_region intron	N/A	NP_001412173.1
	SMOC1	NM_001425245.1		c.1079+7T>A		splice_region intron	N/A	NP_001412174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.1046+7T>A		splice_region intron	N/A	ENSP00000355110.4	Q9H4F8-2
	SMOC1	ENST00000381280.4	TSL:1	c.1046+7T>A		splice_region intron	N/A	ENSP00000370680.4	Q9H4F8-1
	SMOC1	ENST00000853906.1		c.1094+7T>A		splice_region intron	N/A	ENSP00000523965.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30567 AN: 151814 Hom.: 3511 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.153 AC: 38477 AN: 251140 AF XY: 0.146

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.00881

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.160 AC: 233640 AN: 1460912 Hom.: 20354 Cov.: 31 AF XY: 0.156 AC XY: 113388 AN XY: 726832

African (AFR) AF: 0.316 AC: 10576 AN: 33458

American (AMR) AF: 0.161 AC: 7184 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4241 AN: 26132

East Asian (EAS) AF: 0.0233 AC: 926 AN: 39698

South Asian (SAS) AF: 0.0503 AC: 4335 AN: 86248

European-Finnish (FIN) AF: 0.209 AC: 11147 AN: 53306

Middle Eastern (MID) AF: 0.200 AC: 1149 AN: 5750

European-Non Finnish (NFE) AF: 0.166 AC: 184546 AN: 1111246

Other (OTH) AF: 0.158 AC: 9536 AN: 60350

GnomAD4 genome AF: 0.201 AC: 30591 AN: 151932 Hom.: 3509 Cov.: 32 AF XY: 0.198 AC XY: 14678 AN XY: 74262

African (AFR) AF: 0.307 AC: 12700 AN: 41416

American (AMR) AF: 0.171 AC: 2602 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3466

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5164

South Asian (SAS) AF: 0.0439 AC: 211 AN: 4808

European-Finnish (FIN) AF: 0.215 AC: 2267 AN: 10544

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11609 AN: 67964

Other (OTH) AF: 0.192 AC: 405 AN: 2112

Alfa AF: 0.130 Hom.: 481

Bravo AF: 0.205

Asia WGS AF: 0.0650 AC: 229 AN: 3478

EpiCase AF: 0.161

EpiControl AF: 0.157

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 1

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

Other links and lift over

dbSNP: rs1885482; hg19: chr14-70480215; COSMIC: COSV62764027; COSMIC: COSV62764027;