rs2304232

Variant names:

• chr19-41256620-A-G
• rs2304232
• NM_021913.5:c.2196+9A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-41256620-A-G
• chr19-41256620-A-C
• chr19-41256620-A-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_021913.5(AXL):​c.2196+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,610,424 control chromosomes in the GnomAD database, including 17,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1671 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16242 hom.)
• Consequence: AXL NM_021913.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.982
• Publications: 26 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 -16 ACMG points.

• BP6: Variant 19-41256620-A-G is Benign according to our data. Variant chr19-41256620-A-G is described in ClinVar as Benign. ClinVar VariationId is 1261931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXL	NM_021913.5	MANE Select	c.2196+9A>G		intron	N/A	NP_068713.2
	AXL	NM_001699.6		c.2169+9A>G		intron	N/A	NP_001690.2
	AXL	NM_001278599.2		c.1392+9A>G		intron	N/A	NP_001265528.1	M0R0W6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXL	ENST00000301178.9	TSL:1 MANE Select	c.2196+9A>G		intron	N/A	ENSP00000301178.3	P30530-1
	AXL	ENST00000359092.7	TSL:1	c.2169+9A>G		intron	N/A	ENSP00000351995.2	P30530-2
	AXL	ENST00000593513.1	TSL:1	c.1392+9A>G		intron	N/A	ENSP00000471497.1	M0R0W6

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21524 AN: 152006 Hom.: 1672 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.142 AC: 35712 AN: 251090 AF XY: 0.142

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.0941

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.288

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.146 AC: 212628 AN: 1458300 Hom.: 16242 Cov.: 32 AF XY: 0.145 AC XY: 105142 AN XY: 724754

African (AFR) AF: 0.105 AC: 3503 AN: 33414

American (AMR) AF: 0.0988 AC: 4412 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4233 AN: 26112

East Asian (EAS) AF: 0.229 AC: 9044 AN: 39558

South Asian (SAS) AF: 0.0984 AC: 8480 AN: 86204

European-Finnish (FIN) AF: 0.133 AC: 7123 AN: 53362

Middle Eastern (MID) AF: 0.203 AC: 1171 AN: 5758

European-Non Finnish (NFE) AF: 0.149 AC: 165459 AN: 1108998

Other (OTH) AF: 0.153 AC: 9203 AN: 60220

GnomAD4 genome AF: 0.141 AC: 21513 AN: 152124 Hom.: 1671 Cov.: 32 AF XY: 0.139 AC XY: 10368 AN XY: 74366

African (AFR) AF: 0.108 AC: 4473 AN: 41498

American (AMR) AF: 0.129 AC: 1977 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1423 AN: 5168

South Asian (SAS) AF: 0.0992 AC: 478 AN: 4818

European-Finnish (FIN) AF: 0.129 AC: 1363 AN: 10582

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10486 AN: 67992

Other (OTH) AF: 0.153 AC: 323 AN: 2112

Alfa AF: 0.148 Hom.: 3342

Bravo AF: 0.144

Asia WGS AF: 0.193 AC: 674 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.34
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2304232; hg19: chr19-41762525; COSMIC: COSV56563275;