Variant 14-70013498-T-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.1046+7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,612,844 control chromosomes in the GnomAD database, including 23,863 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3509 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20354 hom. )

Consequence

SMOC1
NM_001034852.3 splice_region, intron

Scores

Splicing: ADA: 0.00006533

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.137

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:

SMOC1 (HGNC:):

SMOC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 14-70013498-T-A is Benign according to our data. Variant chr14-70013498-T-A is described in ClinVar as [Benign]. Clinvar id is 257186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SMOC1	NM_001034852.3 linkuse as main transcript	c.1046+7T>A	splice_region_variant, intron_variant	ENST00000361956.8	NP_001030024.1	Q9H4F8-2
SMOC1	NM_022137.6 linkuse as main transcript	c.1046+7T>A	splice_region_variant, intron_variant		NP_071420.1	Q9H4F8-1A0A024R6E0
SMOC1	XM_005267995.2 linkuse as main transcript	c.1079+7T>A	splice_region_variant, intron_variant
SMOC1	XM_005267996.2 linkuse as main transcript	c.1079+7T>A	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8 linkuse as main transcript	c.1046+7T>A		splice_region_variant, intron_variant		1	NM_001034852.3	ENSP00000355110.4		Q9H4F8-2
SMOC1	ENST00000381280.4 linkuse as main transcript	c.1046+7T>A		splice_region_variant, intron_variant		1		ENSP00000370680.4		Q9H4F8-1

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30567

AN:

151814

Hom.:

3511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0170

Gnomad SAS

AF:

0.0441

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.153

AC:

38477

AN:

251140

Hom.:

3586

AF XY:

0.146

AC XY:

19801

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.00881

Gnomad SAS exome

AF:

0.0499

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.160

AC:

233640

AN:

1460912

Hom.:

20354

Cov.:

AF XY:

0.156

AC XY:

113388

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.316

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.0233

Gnomad4 SAS exome

AF:

0.0503

Gnomad4 FIN exome

AF:

0.209

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.201

AC:

30591

AN:

151932

Hom.:

3509

Cov.:

AF XY:

0.198

AC XY:

14678

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.0168

Gnomad4 SAS

AF:

0.0439

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.192

Alfa

AF:

0.130

Hom.:

481

Bravo

AF:

0.205

Asia WGS

AF:

0.0650

AC:

229

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.157

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 17, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000065

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 1

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