19-41220661-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021913.5(AXL):​c.111C>T​(p.Phe37Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,595,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

AXL
NM_021913.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 19-41220661-C-T is Benign according to our data. Variant chr19-41220661-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3610158.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.28 with no splicing effect.
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AXLNM_021913.5 linkc.111C>T p.Phe37Phe synonymous_variant Exon 2 of 20 ENST00000301178.9 NP_068713.2 P30530-1
AXLNM_001699.6 linkc.111C>T p.Phe37Phe synonymous_variant Exon 2 of 19 NP_001690.2 P30530-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AXLENST00000301178.9 linkc.111C>T p.Phe37Phe synonymous_variant Exon 2 of 20 1 NM_021913.5 ENSP00000301178.3 P30530-1
AXLENST00000359092.7 linkc.111C>T p.Phe37Phe synonymous_variant Exon 2 of 19 1 ENSP00000351995.2 P30530-2
AXLENST00000599659.5 linkn.125C>T non_coding_transcript_exon_variant Exon 2 of 12 1
AXLENST00000594880.1 linkn.128C>T non_coding_transcript_exon_variant Exon 2 of 4 4

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152202
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000228
AC:
5
AN:
219456
Hom.:
0
AF XY:
0.0000336
AC XY:
4
AN XY:
118908
show subpopulations
Gnomad AFR exome
AF:
0.000145
Gnomad AMR exome
AF:
0.0000320
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000361
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000104
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000104
AC:
15
AN:
1443784
Hom.:
0
Cov.:
31
AF XY:
0.0000126
AC XY:
9
AN XY:
716980
show subpopulations
Gnomad4 AFR exome
AF:
0.000121
Gnomad4 AMR exome
AF:
0.0000239
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000519
Gnomad4 SAS exome
AF:
0.0000597
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000272
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152202
Hom.:
0
Cov.:
31
AF XY:
0.0000672
AC XY:
5
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.0000340

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jun 19, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
1.5
DANN
Benign
0.67

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1175570418; hg19: chr19-41726566; COSMIC: COSV56571002; COSMIC: COSV56571002; API