chr19-41220549-G-A

Position:

• chr19-41220549-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021913.5(AXL):​c.86-87G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,211,802 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (94 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (46 hom.)
• Consequence: AXL NM_021913.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.656

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 19-41220549-G-A is Benign according to our data. Variant chr19-41220549-G-A is described in ClinVar as [Benign]. Clinvar id is 1280233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXL	NM_021913.5	c.86-87G>A		intron_variant		ENST00000301178.9
AXL	NM_001699.6	c.86-87G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXL	ENST00000301178.9	c.86-87G>A		intron_variant		1	NM_021913.5	A2
AXL	ENST00000359092.7	c.86-87G>A		intron_variant		1		P2
AXL	ENST00000599659.5	n.100-87G>A		intron_variant, non_coding_transcript_variant		1
AXL	ENST00000594880.1	n.102+48G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2755 AN: 152160 Hom.: 91 Cov.: 31

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00208 AC: 2201 AN: 1059524 Hom.: 46 Cov.: 15 AF XY: 0.00193 AC XY: 1016 AN XY: 526270

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.00331

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000246

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000331

Gnomad4 OTH exome AF: 0.00512

GnomAD4 genome AF: 0.0182 AC: 2774 AN: 152278 Hom.: 94 Cov.: 31 AF XY: 0.0183 AC XY: 1365 AN XY: 74470

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0171 Hom.: 11

Bravo AF: 0.0198

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.63
CADD	Benign	10
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs73931453; hg19: chr19-41726454;