chr19-41234990-T-C

Variant names:

• chr19-41234990-T-C
• rs4802113
• NM_021913.5:c.784-2954T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021913.5(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 NM_021913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AXL	NM_021913.5	c.784-2954T>C		intron_variant	Intron 6 of 19	ENST00000301178.9	NP_068713.2
AXL	NM_001699.6	c.784-2954T>C		intron_variant	Intron 6 of 18		NP_001690.2
AXL	NM_001278599.2	c.-21-2954T>C		intron_variant	Intron 3 of 16		NP_001265528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXL	ENST00000301178.9	c.784-2954T>C		intron_variant	Intron 6 of 19	1	NM_021913.5	ENSP00000301178.3
AXL	ENST00000359092.7	c.784-2954T>C		intron_variant	Intron 6 of 18	1		ENSP00000351995.2
AXL	ENST00000593513.1	c.-21-2954T>C		intron_variant	Intron 3 of 16	1		ENSP00000471497.1
AXL	ENST00000599659.5	n.798-2954T>C		intron_variant	Intron 6 of 11	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

African (AFR) AF: 0.670 AC: 27784 AN: 41466

American (AMR) AF: 0.415 AC: 6339 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1531 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2135 AN: 5168

South Asian (SAS) AF: 0.615 AC: 2969 AN: 4824

European-Finnish (FIN) AF: 0.417 AC: 4388 AN: 10532

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30563 AN: 67926

Other (OTH) AF: 0.486 AC: 1028 AN: 2114

Alfa AF: 0.485 Hom.: 3046

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
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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