rs11626232

Variant names:

• chr14-70020679-C-T
• rs11626232
• NM_001034852.3:c.1047-2524C>T

Variant summary

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

The NM_001034852.3(SMOC1):​c.1047-2524C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,114 control chromosomes in the GnomAD database, including 1,011 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 0.11 (1011 hom., cov: 32)
• Consequence: SMOC1 NM_001034852.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC1	NM_001034852.3	c.1047-2524C>T		intron_variant	Intron 10 of 11	ENST00000361956.8	NP_001030024.1
SMOC1	NM_001425244.1	c.1080-2524C>T		intron_variant	Intron 10 of 11		NP_001412173.1
SMOC1	NM_001425245.1	c.1080-2524C>T		intron_variant	Intron 10 of 11		NP_001412174.1
SMOC1	NM_022137.6	c.1047-2524C>T		intron_variant	Intron 10 of 11		NP_071420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8	c.1047-2524C>T		intron_variant	Intron 10 of 11	1	NM_001034852.3	ENSP00000355110.4
SMOC1	ENST00000381280.4	c.1047-2524C>T		intron_variant	Intron 10 of 11	1		ENSP00000370680.4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16328 AN: 151996 Hom.: 1010 Cov.: 32

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.107 AC: 16327 AN: 152114 Hom.: 1011 Cov.: 32 AF XY: 0.102 AC XY: 7584 AN XY: 74368

African (AFR) AF: 0.0730 AC: 3029 AN: 41498

American (AMR) AF: 0.0952 AC: 1456 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5162

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4808

European-Finnish (FIN) AF: 0.107 AC: 1133 AN: 10584

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9603 AN: 67992

Other (OTH) AF: 0.124 AC: 262 AN: 2106

Alfa AF: 0.118 Hom.: 148

Bravo AF: 0.106

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.052
DANN	Benign	0.31
PhyloP100		-2.7
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: rs11626232; hg19: chr14-70487396;