Variant chr5-70925081-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001297715.1(SMN1):c.-23C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.036 ( 4 hom., cov: 1)

Exomes 𝑓: 0.0097 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

SMN1
NM_001297715.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0780

Variant links:

Genes affected

SMN1 (HGNC:11117): (survival of motor neuron 1, telomeric) This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. The telomeric and centromeric copies of this gene are nearly identical and encode the same protein. However, mutations in this gene, the telomeric copy, are associated with spinal muscular atrophy; mutations in the centromeric copy do not lead to disease. The centromeric copy may be a modifier of disease caused by mutation in the telomeric copy. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. Note that the nine exons of both the telomeric and centromeric copies are designated historically as exon 1, 2a, 2b, and 3-8. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene. The protein encoded by this gene localizes to both the cytoplasm and the nucleus. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). This protein forms heteromeric complexes with proteins such as SIP1 and GEMIN4, and also interacts with several proteins known to be involved in the biogenesis of snRNPs, such as hnRNP U protein and the small nucleolar RNA binding protein. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2014]

SMN1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-70925081-C-G is Benign according to our data. Variant chr5-70925081-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1217482.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMN1	NM_000344.4 linkuse as main transcript	c.-23C>G		upstream_gene_variant		ENST00000380707.9	NP_000335.1	Q16637-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMN1	ENST00000380707.9 linkuse as main transcript	c.-23C>G		upstream_gene_variant		1	NM_000344.4	ENSP00000370083.4		Q16637-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

153

AN:

4308

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.0429

GnomAD3 exomes

AF:

0.0204

AC:

100

AN:

4902

Hom.:

AF XY:

0.0164

AC XY:

AN XY:

2628

show subpopulations

Gnomad AFR exome

AF:

0.0791

Gnomad AMR exome

AF:

0.00495

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00694

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00970

AC:

290

AN:

29898

Hom.:

Cov.:

AF XY:

0.00823

AC XY:

131

AN XY:

15918

show subpopulations

Gnomad4 AFR exome

AF:

0.0832

Gnomad4 AMR exome

AF:

0.00792

Gnomad4 ASJ exome

AF:

0.00164

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000427

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000372

Gnomad4 OTH exome

AF:

0.00959

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0361

AC:

156

AN:

4316

Hom.:

Cov.:

AF XY:

0.0377

AC XY:

AN XY:

1912

show subpopulations

Gnomad4 AFR

AF:

0.0521

Gnomad4 AMR

AF:

0.0246

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.0441

Alfa

AF:

0.0175

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.6

DANN

Benign

0.88

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