chr19-41219366-A-G

Position:

• chr19-41219366-A-G

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.-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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.462

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=-0.61).
• 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	c.-27A>G		5_prime_UTR_variant	1/20	ENST00000301178.9
AXL	NM_001699.6	c.-27A>G		5_prime_UTR_variant	1/19

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76400 AN: 151810 Hom.: 19476 Cov.: 31

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

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.: 34 AF XY: 0.488 AC XY: 340327 AN XY: 697736

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.: 31 AF XY: 0.502 AC XY: 37267 AN XY: 74252

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

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	18
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

Other links and lift over

dbSNP: rs10411012; hg19: chr19-41725271;