chr14-69877067-T-C

Variant names:

• chr14-69877067-T-C
• rs10162517
• ENST00000831801.1:n.50A>G

Variant summary

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

The ENST00000831801.1(ENSG00000308116):​n.50A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,040 control chromosomes in the GnomAD database, including 7,497 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 0.31 (7497 hom., cov: 32)
• Consequence: ENSG00000308116 ENST00000831801.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 4 publications found

Genes affected

ENSG00000308116 (HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000308116	ENST00000831801.1	n.50A>G		non_coding_transcript_exon_variant	Exon 1 of 2
SMOC1	ENST00000555917.1	n.404+12853T>C		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47133 AN: 151922 Hom.: 7488 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.310 AC: 47179 AN: 152040 Hom.: 7497 Cov.: 32 AF XY: 0.311 AC XY: 23097 AN XY: 74330

African (AFR) AF: 0.262 AC: 10855 AN: 41466

American (AMR) AF: 0.329 AC: 5023 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1073 AN: 5168

South Asian (SAS) AF: 0.394 AC: 1898 AN: 4818

European-Finnish (FIN) AF: 0.340 AC: 3595 AN: 10576

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23069 AN: 67948

Other (OTH) AF: 0.295 AC: 622 AN: 2110

Alfa AF: 0.325 Hom.: 10752

Bravo AF: 0.298

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.18
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs10162517; hg19: chr14-70343784;