rs3742908

Variant names:

• chr14-69879273-T-A
• rs3742908
• ENST00000555917.1:n.404+15059T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000555917.1(SMOC1):​n.404+15059T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 167,176 control chromosomes in the GnomAD database, including 2,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (2886 hom., cov: 32)
  • Exomes 𝑓: 0.040 (37 hom.)
• Consequence: SMOC1 ENST00000555917.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.257
• 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, 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=-0.64).
• BP6: Variant 14-69879273-T-A is Benign according to our data. Variant chr14-69879273-T-A is described in ClinVar as Benign. ClinVar VariationId is 1285868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

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.-406T>A		upstream_gene	N/A	NP_001030024.1	Q9H4F8-2
	SMOC1	NM_001425244.1		c.-406T>A		upstream_gene	N/A	NP_001412173.1
	SMOC1	NM_001425245.1		c.-406T>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+15059T>A		intron	N/A
	SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.-406T>A		upstream_gene	N/A	ENSP00000355110.4	Q9H4F8-2
	SMOC1	ENST00000381280.4	TSL:1	c.-406T>A		upstream_gene	N/A	ENSP00000370680.4	Q9H4F8-1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19272 AN: 151844 Hom.: 2880 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0305

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0953

GnomAD4 exome AF: 0.0398 AC: 606 AN: 15212 Hom.: 37 AF XY: 0.0404 AC XY: 308 AN XY: 7624

African (AFR) AF: 0.304 AC: 177 AN: 582

American (AMR) AF: 0.0385 AC: 13 AN: 338

Ashkenazi Jewish (ASJ) AF: 0.0474 AC: 26 AN: 548

East Asian (EAS) AF: 0.0423 AC: 30 AN: 710

South Asian (SAS) AF: 0.149 AC: 28 AN: 188

European-Finnish (FIN) AF: 0.0240 AC: 19 AN: 792

Middle Eastern (MID) AF: 0.0897 AC: 7 AN: 78

European-Non Finnish (NFE) AF: 0.0236 AC: 259 AN: 10980

Other (OTH) AF: 0.0472 AC: 47 AN: 996

GnomAD4 genome AF: 0.127 AC: 19315 AN: 151964 Hom.: 2886 Cov.: 32 AF XY: 0.126 AC XY: 9390 AN XY: 74304

African (AFR) AF: 0.359 AC: 14878 AN: 41406

American (AMR) AF: 0.0566 AC: 866 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 185 AN: 3466

East Asian (EAS) AF: 0.0284 AC: 146 AN: 5146

South Asian (SAS) AF: 0.179 AC: 861 AN: 4816

European-Finnish (FIN) AF: 0.0305 AC: 323 AN: 10584

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1834 AN: 67942

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

Alfa AF: 0.0807 Hom.: 201

Bravo AF: 0.135

Asia WGS AF: 0.113 AC: 394 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	-0.64
CADD	Benign	9.0
DANN	Benign	0.72
PhyloP100		-0.26
PromoterAI		0.11	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3742908; hg19: chr14-70345990;