rs4802113

Positions:

• chr19-41234990-T-C
• chr19-41234990-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000301178.9(AXL):​c.784-2954T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,972 control chromosomes in the GnomAD database, including 20,734 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20734 hom., cov: 31)
• Consequence: AXL ENST00000301178.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXL	NM_021913.5	c.784-2954T>C		intron_variant		ENST00000301178.9	NP_068713.2
AXL	NM_001278599.2	c.-21-2954T>C		intron_variant			NP_001265528.1
AXL	NM_001699.6	c.784-2954T>C		intron_variant			NP_001690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXL	ENST00000301178.9	c.784-2954T>C		intron_variant		1	NM_021913.5	ENSP00000301178	A2
AXL	ENST00000359092.7	c.784-2954T>C		intron_variant		1		ENSP00000351995	P2
AXL	ENST00000593513.1	c.-21-2954T>C		intron_variant		1		ENSP00000471497
AXL	ENST00000599659.5	n.798-2954T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77404 AN: 151854 Hom.: 20697 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77480 AN: 151972 Hom.: 20734 Cov.: 31 AF XY: 0.509 AC XY: 37828 AN XY: 74268

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.486

Alfa AF: 0.480 Hom.: 2885

Bravo AF: 0.513

Asia WGS AF: 0.561 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.40

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: rs4802113; hg19: chr19-41740895; COSMIC: COSV56566576;