Variant 19-41219505-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_021913.5(AXL):c.85+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,583,376 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 81 hom., cov: 30)

Exomes 𝑓: 0.0020 ( 83 hom. )

Consequence

AXL
NM_021913.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.128

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=-0.83).

BP6

Variant 19-41219505-G-A is Benign according to our data. Variant chr19-41219505-G-A is described in ClinVar as [Benign]. Clinvar id is 1248203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0579 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.85+28G>A		intron_variant		ENST00000301178.9
AXL	NM_001699.6 linkuse as main transcript	c.85+28G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
AXL	ENST00000301178.9 linkuse as main transcript	c.85+28G>A	intron_variant	1	NM_021913.5	A2	P30530-1
AXL	ENST00000359092.7 linkuse as main transcript	c.85+28G>A	intron_variant	1		P2	P30530-2
AXL	ENST00000599659.5 linkuse as main transcript	n.99+28G>A	intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2636

AN:

151760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0599

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00754

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.0106

GnomAD3 exomes

AF:

0.00492

AC:

921

AN:

187038

Hom.:

AF XY:

0.00401

AC XY:

408

AN XY:

101764

show subpopulations

Gnomad AFR exome

AF:

0.0734

Gnomad AMR exome

AF:

0.00361

Gnomad ASJ exome

AF:

0.00285

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000348

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00199

AC:

2844

AN:

1431500

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1221

AN XY:

709490

show subpopulations

Gnomad4 AFR exome

AF:

0.0652

Gnomad4 AMR exome

AF:

0.00401

Gnomad4 ASJ exome

AF:

0.00231

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.000183

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.0174

AC:

2639

AN:

151876

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1245

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.0598

Gnomad4 AMR

AF:

0.00753

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000833

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.0105

Alfa

AF:

0.00884

Hom.:

Bravo

AF:

0.0206

Asia WGS

AF:

0.00346

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 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.0

DANN

Benign

0.85

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