dbSNP rs2304234: AXL:c.1313-35T>C (chr19-41242848-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0550

Publications

20 publications found

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]

AXL links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_021913.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021913.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AXL	NM_021913.5	MANE Select	c.1313-35T>C	intron	N/A	NP_068713.2
AXL	NM_001699.6		c.1286-35T>C	intron	N/A	NP_001690.2
AXL	NM_001278599.2		c.509-35T>C	intron	N/A	NP_001265528.1	M0R0W6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AXL	ENST00000301178.9	TSL:1 MANE Select	c.1313-35T>C	intron	N/A	ENSP00000301178.3	P30530-1
AXL	ENST00000359092.7	TSL:1	c.1286-35T>C	intron	N/A	ENSP00000351995.2	P30530-2
AXL	ENST00000593513.1	TSL:1	c.509-35T>C	intron	N/A	ENSP00000471497.1	M0R0W6

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70124

AN:

151938

Hom.:

17041

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.402

AC:

100505

AN:

250084

AF XY:

0.405

show subpopulations

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 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.:

AF XY:

0.416

AC XY:

301734

AN XY:

725762

show subpopulations

African (AFR)

AF:

0.613

AC:

20497

AN:

33422

American (AMR)

AF:

0.292

AC:

13015

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

9343

AN:

26058

East Asian (EAS)

AF:

0.302

AC:

11963

AN:

39644

South Asian (SAS)

AF:

0.429

AC:

36932

AN:

86162

European-Finnish (FIN)

AF:

0.393

AC:

20966

AN:

53286

Middle Eastern (MID)

AF:

0.434

AC:

2499

AN:

5754

European-Non Finnish (NFE)

AF:

0.419

AC:

465720

AN:

1110196

Other (OTH)

AF:

0.427

AC:

25735

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

16601

33202

49803

66404

83005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14382

28764

43146

57528

71910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.462

AC:

70194

AN:

152056

Hom.:

17078

Cov.:

AF XY:

0.458

AC XY:

34009

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.614

AC:

25449

AN:

41460

American (AMR)

AF:

0.365

AC:

5576

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

1305

AN:

3470

East Asian (EAS)

AF:

0.351

AC:

1811

AN:

5160

South Asian (SAS)

AF:

0.432

AC:

2080

AN:

4818

European-Finnish (FIN)

AF:

0.387

AC:

4094

AN:

10588

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28249

AN:

67968

Other (OTH)

AF:

0.429

AC:

907

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1903

3806

5709

7612

9515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.434

Hom.:

30494

Bravo

AF:

0.468

Asia WGS

AF:

0.406

AC:

1412

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

9.5

(source)

DANN

Benign

0.68

PhyloP100

-0.055

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over