5-132060983-A-G

Position:

• chr5-132060983-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000588.4(IL3):​c.179A>G​(p.Asn60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,614,044 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (13 hom.)
• Consequence: IL3 NM_000588.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24

Genes affected

IL3 (HGNC:6011): (interleukin 3) The protein encoded by this gene is a potent growth promoting cytokine. This cytokine is capable of supporting the proliferation of a broad range of hematopoietic cell types. It is involved in a variety of cell activities such as cell growth, differentiation and apoptosis. This cytokine has been shown to also possess neurotrophic activity, and it may be associated with neurologic disorders. [provided by RefSeq, Jul 2008]

LOC105379174 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047552586).
• BP6: Variant 5-132060983-A-G is Benign according to our data. Variant chr5-132060983-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 720302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 284 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL3	NM_000588.4	c.179A>G	p.Asn60Ser	missense_variant	2/5	ENST00000296870.3
LOC105379174	XR_001742531.2	n.211+488T>C		intron_variant, non_coding_transcript_variant
LOC105379174	XR_948784.3	n.398+488T>C		intron_variant, non_coding_transcript_variant
LOC105379174	XR_948785.3	n.228+488T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL3	ENST00000296870.3	c.179A>G	p.Asn60Ser	missense_variant	2/5	1	NM_000588.4	P1

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 285 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00169 AC: 425 AN: 251366 Hom.: 3 AF XY: 0.00174 AC XY: 237 AN XY: 135852

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00284

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00301 AC: 4399 AN: 1461762 Hom.: 13 Cov.: 32 AF XY: 0.00289 AC XY: 2103 AN XY: 727192

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.000431

Gnomad4 NFE exome AF: 0.00371

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.00157 AC XY: 117 AN XY: 74460

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00265 Hom.: 0

Bravo AF: 0.00240

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00337 AC: 29

ExAC AF: 0.00163 AC: 198

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00267

EpiControl AF: 0.00314

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.46
DANN	Benign	0.81
DEOGEN2	Benign	0.38	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.032
Sift	Uncertain	0.025	D
Sift4G	Benign	0.20	T
Polyphen		0.048	B
Vest4		0.033
MVP		0.11
MPC		0.23
ClinPred		0.0031	T
GERP RS		-5.8
Varity_R		0.11
gMVP		0.39

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: rs35482671; hg19: chr5-131396676;