Variant 19-41219366-A-G 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_021913.5(AXL):c.-27A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,563,788 control chromosomes in the GnomAD database, including 186,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19488 hom., cov: 31)

Exomes 𝑓: 0.49 ( 167248 hom. )

Consequence

AXL
NM_021913.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.462

Variant links:

Genes affected

AXL (HGNC:905): (AXL receptor tyrosine kinase) The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. The encoded protein possesses an extracellular domain which is composed of two immunoglobulin-like motifs at the N-terminal, followed by two fibronectin type-III motifs. It transduces signals from the extracellular matrix into the cytoplasm by binding to the vitamin K-dependent protein growth arrest-specific 6 (Gas6). This gene may be involved in several cellular functions including growth, migration, aggregation and anti-inflammation in multiple cell types. The encoded protein acts as a host cell receptor for multiple viruses, including Marburg, Ebola and Lassa viruses and is a candidate receptor for the SARS-CoV2 virus. [provided by RefSeq, Sep 2021]

AXL 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=-0.61).

BP6

Variant 19-41219366-A-G is Benign according to our data. Variant chr19-41219366-A-G is described in ClinVar as [Benign]. Clinvar id is 1248751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXL	NM_021913.5 linkuse as main transcript	c.-27A>G		5_prime_UTR_variant	1/20	ENST00000301178.9
AXL	NM_001699.6 linkuse as main transcript	c.-27A>G		5_prime_UTR_variant	1/19

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXL	ENST00000301178.9 linkuse as main transcript	c.-27A>G	5_prime_UTR_variant	1/20	1	NM_021913.5	A2	P30530-1
AXL	ENST00000359092.7 linkuse as main transcript	c.-27A>G	5_prime_UTR_variant	1/19	1		P2	P30530-2
AXL	ENST00000599659.5 linkuse as main transcript		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76400

AN:

151810

Hom.:

19476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.593

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.571

Gnomad FIN

AF:

0.493

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.483

GnomAD3 exomes

AF:

0.465

AC:

80969

AN:

173972

Hom.:

19444

AF XY:

0.475

AC XY:

44584

AN XY:

93782

show subpopulations

Gnomad AFR exome

AF:

0.586

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.387

Gnomad SAS exome

AF:

0.574

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.481

Gnomad OTH exome

AF:

0.462

GnomAD4 exome

AF:

0.485

AC:

684902

AN:

1411860

Hom.:

167248

Cov.:

AF XY:

0.488

AC XY:

340327

AN XY:

697736

show subpopulations

Gnomad4 AFR exome

AF:

0.593

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.452

Gnomad4 EAS exome

AF:

0.403

Gnomad4 SAS exome

AF:

0.570

Gnomad4 FIN exome

AF:

0.489

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.481

GnomAD4 genome

AF:

0.503

AC:

76445

AN:

151928

Hom.:

19488

Cov.:

AF XY:

0.502

AC XY:

37267

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.593

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.383

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.493

Gnomad4 NFE

AF:

0.489

Gnomad4 OTH

AF:

0.480

Alfa

AF:

0.487

Hom.:

3844

Bravo

AF:

0.493

Asia WGS

AF:

0.478

AC:

1661

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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.83

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