Variant 14-70011466-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001034852.3(SMOC1):c.858-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,561,566 control chromosomes in the GnomAD database, including 35,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2679 hom., cov: 30)

Exomes 𝑓: 0.20 ( 32564 hom. )

Consequence

SMOC1
NM_001034852.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.735

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-70011466-C-A is Benign according to our data. Variant chr14-70011466-C-A is described in ClinVar as [Benign]. Clinvar id is 257190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SMOC1	NM_001034852.3 linkuse as main transcript	c.858-19C>A	intron_variant	ENST00000361956.8	NP_001030024.1
SMOC1	NM_022137.6 linkuse as main transcript	c.858-19C>A	intron_variant		NP_071420.1
SMOC1	XM_005267995.2 linkuse as main transcript	c.891-19C>A	intron_variant		XP_005268052.1
SMOC1	XM_005267996.2 linkuse as main transcript	c.891-19C>A	intron_variant		XP_005268053.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8 linkuse as main transcript	c.858-19C>A	intron_variant	1	NM_001034852.3	ENSP00000355110	A2	Q9H4F8-2
SMOC1	ENST00000381280.4 linkuse as main transcript	c.858-19C>A	intron_variant	1		ENSP00000370680	P4	Q9H4F8-1
SMOC1	ENST00000557483.1 linkuse as main transcript	n.436-19C>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24138

AN:

150564

Hom.:

2672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.211

AC:

52951

AN:

251110

Hom.:

6666

AF XY:

0.208

AC XY:

28197

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.411

Gnomad SAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.200

AC:

282363

AN:

1410884

Hom.:

32564

Cov.:

AF XY:

0.200

AC XY:

140833

AN XY:

704368

show subpopulations

Gnomad4 AFR exome

AF:

0.0349

Gnomad4 AMR exome

AF:

0.337

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.196

GnomAD4 genome

AF:

0.160

AC:

24148

AN:

150682

Hom.:

2679

Cov.:

AF XY:

0.166

AC XY:

12198

AN XY:

73484

show subpopulations

Gnomad4 AFR

AF:

0.0410

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.404

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.169

Hom.:

452

Bravo

AF:

0.162

Asia WGS

AF:

0.254

AC:

880

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Microphthalmia with limb anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.46

DANN

Benign

0.66

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over