14-69879273-T-A

Position:

• chr14-69879273-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000555917.1(SMOC1):​n.404+15059T>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.257

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000555917.1	n.404+15059T>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.0474

Gnomad4 EAS exome AF: 0.0423

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0240

Gnomad4 NFE exome AF: 0.0236

Gnomad4 OTH exome AF: 0.0472

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

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.0534

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0305

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0942

Alfa AF: 0.0807 Hom.: 201

Bravo AF: 0.135

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.0
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3742908; hg19: chr14-70345990;