Variant 14-50587757-G-C 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_015915.5(ATL1):c.35-74G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 1,591,626 control chromosomes in the GnomAD database, including 1,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 104 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1653 hom. )

Consequence

ATL1
NM_015915.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.387

Variant links:

Genes affected

ATL1 (HGNC:11231): (atlastin GTPase 1) The protein encoded by this gene is a GTPase and a Golgi body transmembrane protein. The encoded protein can form a homotetramer and has been shown to interact with spastin and with mitogen-activated protein kinase kinase kinase kinase 4. This protein may be involved in axonal maintenance as evidenced by the fact that defects in this gene are a cause of spastic paraplegia type 3. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ATL1 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=-0.89).

BP6

Variant 14-50587757-G-C is Benign according to our data. Variant chr14-50587757-G-C is described in ClinVar as [Benign]. Clinvar id is 1262532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ATL1	NM_015915.5 linkuse as main transcript	c.35-74G>C	intron_variant	ENST00000358385.12
ATL1	NM_001127713.1 linkuse as main transcript	c.35-74G>C	intron_variant
ATL1	NM_181598.4 linkuse as main transcript	c.35-74G>C	intron_variant
ATL1	XM_047431430.1 linkuse as main transcript	c.35-74G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATL1	ENST00000358385.12 linkuse as main transcript	c.35-74G>C		intron_variant		1	NM_015915.5	P3	Q8WXF7-1

Frequencies

GnomAD3 genomes

AF:

0.0375

AC:

5711

AN:

152132

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.0396

Gnomad ASJ

AF:

0.0386

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0368

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0488

Gnomad OTH

AF:

0.0459

GnomAD4 exome

AF:

0.0439

AC:

63209

AN:

1439376

Hom.:

1653

AF XY:

0.0435

AC XY:

31249

AN XY:

717642

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.0281

Gnomad4 ASJ exome

AF:

0.0384

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.0499

Gnomad4 OTH exome

AF:

0.0402

GnomAD4 genome

AF:

0.0376

AC:

5720

AN:

152250

Hom.:

104

Cov.:

AF XY:

0.0374

AC XY:

2783

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0247

Gnomad4 AMR

AF:

0.0395

Gnomad4 ASJ

AF:

0.0386

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0368

Gnomad4 NFE

AF:

0.0488

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0232

Hom.:

Bravo

AF:

0.0362

Asia WGS

AF:

0.0140

AC:

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.42

DANN

Benign

0.41

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