5-132543371-C-A

Variant names:

• chr5-132543371-C-A
• rs112946922
• NM_000879.3:c.108G>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000879.3(IL5):​c.108G>T​(p.Leu36Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,614,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: IL5 NM_000879.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.117
• Publications: 1 publications found

Genes affected

IL5 (HGNC:6016): (interleukin 5) This gene encodes a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. The encoded cytokine plays a major role in the regulation of eosinophil formation, maturation, recruitment and survival. The increased production of this cytokine may be related to pathogenesis of eosinophil-dependent inflammatory diseases. This cytokine functions by binding to its receptor, which is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). This gene is located on chromosome 5 within a cytokine gene cluster which includes interleukin 4 (IL4), interleukin 13 (IL13), and CSF2 . This gene, IL4, and IL13 may be regulated coordinately by long-range regulatory elements spread over 120 kilobases on chromosome 5q31. [provided by RefSeq, Jul 2013]

ENSG00000283782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-132543371-C-A is Benign according to our data. Variant chr5-132543371-C-A is described in ClinVar as [Benign]. Clinvar id is 717850.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.117 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5	NM_000879.3	c.108G>T	p.Leu36Leu	synonymous_variant	Exon 1 of 4	ENST00000231454.6	NP_000870.1
IL5	XM_005271988.5	c.174G>T	p.Leu58Leu	synonymous_variant	Exon 2 of 5		XP_005272045.1
IL5	XM_011543373.4	c.108G>T	p.Leu36Leu	synonymous_variant	Exon 3 of 6		XP_011541675.1
IL5	XM_047417148.1	c.43-245G>T		intron_variant	Intron 1 of 3		XP_047273104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL5	ENST00000231454.6	c.108G>T	p.Leu36Leu	synonymous_variant	Exon 1 of 4	1	NM_000879.3	ENSP00000231454.1
ENSG00000283782	ENST00000638452.2	c.-168-15913C>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 164 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000251 AC: 63 AN: 251342 AF XY: 0.000155

Gnomad AFR exome AF: 0.00369

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000110 AC: 161 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 78 AN XY: 727228

African (AFR) AF: 0.00388 AC: 130 AN: 33476

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.000381 AC: 23 AN: 60392

GnomAD4 genome AF: 0.00110 AC: 167 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.00110 AC XY: 82 AN XY: 74490

African (AFR) AF: 0.00392 AC: 163 AN: 41568

American (AMR) AF: 0.000261 AC: 4 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000350 Hom.: 0

Bravo AF: 0.00112

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.5
DANN	Benign	0.55
PhyloP100		0.12
PromoterAI		-0.016	Neutral

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: rs112946922; hg19: chr5-131879063;