chr19-41242848-T-C

Position:

• chr19-41242848-T-C

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.1313-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,611,472 control chromosomes in the GnomAD database, including 145,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17078 hom., cov: 32)
  • Exomes 𝑓: 0.42 (128259 hom.)
• Consequence: AXL NM_021913.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0550

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=-0.91).
• BP6: Variant 19-41242848-T-C is Benign according to our data. Variant chr19-41242848-T-C is described in ClinVar as [Benign]. Clinvar id is 1236802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXL	NM_021913.5	c.1313-35T>C		intron_variant		ENST00000301178.9
AXL	NM_001278599.2	c.509-35T>C		intron_variant
AXL	NM_001699.6	c.1286-35T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXL	ENST00000301178.9	c.1313-35T>C		intron_variant		1	NM_021913.5	A2
AXL	ENST00000359092.7	c.1286-35T>C		intron_variant		1		P2
AXL	ENST00000593513.1	c.509-35T>C		intron_variant		1
AXL	ENST00000599659.5	n.1327-35T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70124 AN: 151938 Hom.: 17041 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.434

GnomAD3 exomes AF: 0.402 AC: 100505 AN: 250084 Hom.: 21091 AF XY: 0.405 AC XY: 54634 AN XY: 135050

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.359

Gnomad SAS exome AF: 0.429

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.413

Gnomad OTH exome AF: 0.406

GnomAD4 exome AF: 0.416 AC: 606670 AN: 1459416 Hom.: 128259 Cov.: 37 AF XY: 0.416 AC XY: 301734 AN XY: 725762

Gnomad4 AFR exome AF: 0.613

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.462 AC: 70194 AN: 152056 Hom.: 17078 Cov.: 32 AF XY: 0.458 AC XY: 34009 AN XY: 74322

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.429

Alfa AF: 0.419 Hom.: 18225

Bravo AF: 0.468

Asia WGS AF: 0.406 AC: 1412 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	-0.91
CADD	Benign	9.5
DANN	Benign	0.68

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: rs2304234; hg19: chr19-41748753; COSMIC: COSV56565459;