Variant chr14-69879633-G-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.-46G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,389,404 control chromosomes in the GnomAD database, including 5,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 323 hom., cov: 33)

Exomes 𝑓: 0.083 ( 4931 hom. )

Consequence

SMOC1
NM_001034852.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.24

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=-0.73).

BP6

Variant 14-69879633-G-A is Benign according to our data. Variant chr14-69879633-G-A is described in ClinVar as [Benign]. Clinvar id is 1230923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SMOC1	NM_001034852.3 linkuse as main transcript	c.-46G>A	5_prime_UTR_variant	1/12	ENST00000361956.8	NP_001030024.1
SMOC1	NM_022137.6 linkuse as main transcript	c.-46G>A	5_prime_UTR_variant	1/12		NP_071420.1
SMOC1	XM_005267995.2 linkuse as main transcript	c.-46G>A	5_prime_UTR_variant	1/12		XP_005268052.1
SMOC1	XM_005267996.2 linkuse as main transcript	c.-46G>A	5_prime_UTR_variant	1/12		XP_005268053.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8 linkuse as main transcript	c.-46G>A	5_prime_UTR_variant	1/12	1	NM_001034852.3	ENSP00000355110	A2	Q9H4F8-2
SMOC1	ENST00000381280.4 linkuse as main transcript	c.-46G>A	5_prime_UTR_variant	1/12	1		ENSP00000370680	P4	Q9H4F8-1
SMOC1	ENST00000555917.1 linkuse as main transcript	n.404+15419G>A	intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8100

AN:

152108

Hom.:

323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0516

Gnomad ASJ

AF:

0.0643

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0319

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0853

Gnomad OTH

AF:

0.0564

GnomAD3 exomes

AF:

0.0684

AC:

3063

AN:

44762

Hom.:

156

AF XY:

0.0662

AC XY:

1768

AN XY:

26704

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.0512

Gnomad ASJ exome

AF:

0.0772

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0196

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0784

GnomAD4 exome

AF:

0.0835

AC:

103303

AN:

1237186

Hom.:

4931

Cov.:

AF XY:

0.0819

AC XY:

49767

AN XY:

607548

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.0492

Gnomad4 ASJ exome

AF:

0.0668

Gnomad4 EAS exome

AF:

0.0000365

Gnomad4 SAS exome

AF:

0.0161

Gnomad4 FIN exome

AF:

0.0393

Gnomad4 NFE exome

AF:

0.0947

Gnomad4 OTH exome

AF:

0.0692

GnomAD4 genome

AF:

0.0532

AC:

8098

AN:

152218

Hom.:

323

Cov.:

AF XY:

0.0495

AC XY:

3688

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.0514

Gnomad4 ASJ

AF:

0.0643

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0319

Gnomad4 NFE

AF:

0.0853

Gnomad4 OTH

AF:

0.0558

Alfa

AF:

0.0645

Hom.:

Bravo

AF:

0.0537

Asia WGS

AF:

0.0100

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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