chr5-132556665-C-T

Variant names:

• chr5-132556665-C-T
• rs2706335
• ENST00000640655.2:c.-168-2619C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000416135.5(RAD50):​c.-169+192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,236,734 control chromosomes in the GnomAD database, including 611,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (72128 hom., cov: 31)
  • Exomes 𝑓: 1.0 (539710 hom.)
• Consequence: RAD50 ENST00000416135.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93

Genes affected

ENSG00000283782 (HGNC:):

RAD50 (HGNC:9816): (RAD50 double strand break repair protein) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-132556665-C-T is Benign according to our data. Variant chr5-132556665-C-T is described in ClinVar as [Benign]. Clinvar id is 1288553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL5	XM_005271988.5	c.42+9G>A		intron_variant	Intron 1 of 4		XP_005272045.1
IL5	XM_011543373.4	c.-127+9G>A		intron_variant	Intron 1 of 5		XP_011541675.1
IL5	XM_047417148.1	c.42+9G>A		intron_variant	Intron 1 of 3		XP_047273104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283782	ENST00000640655.2	c.-168-2619C>T		intron_variant	Intron 2 of 25	5		ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147963 AN: 152188 Hom.: 72073 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.985

GnomAD2 exomes AF: 0.994 AC: 88810 AN: 89310 AF XY: 0.996

Gnomad AFR exome AF: 0.856

Gnomad AMR exome AF: 0.994

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.998 AC: 1081785 AN: 1084428 Hom.: 539710 Cov.: 24 AF XY: 0.998 AC XY: 524076 AN XY: 525192

Gnomad4 AFR exome AF: 0.892 AC: 18346 AN: 20558

Gnomad4 AMR exome AF: 0.994 AC: 16707 AN: 16812

Gnomad4 ASJ exome AF: 1.00 AC: 14096 AN: 14096

Gnomad4 EAS exome AF: 1.00 AC: 11536 AN: 11536

Gnomad4 SAS exome AF: 1.00 AC: 62223 AN: 62236

Gnomad4 FIN exome AF: 1.00 AC: 25904 AN: 25904

Gnomad4 NFE exome AF: 1.00 AC: 889481 AN: 889574

Gnomad4 Remaining exome AF: 0.995 AC: 39256 AN: 39452

GnomAD4 genome AF: 0.972 AC: 148076 AN: 152306 Hom.: 72128 Cov.: 31 AF XY: 0.974 AC XY: 72510 AN XY: 74478

Gnomad4 AFR AF: 0.903 AC: 0.903164 AN: 0.903164

Gnomad4 AMR AF: 0.990 AC: 0.989805 AN: 0.989805

Gnomad4 ASJ AF: 1.00 AC: 1 AN: 1

Gnomad4 EAS AF: 1.00 AC: 1 AN: 1

Gnomad4 SAS AF: 1.00 AC: 0.999586 AN: 0.999586

Gnomad4 FIN AF: 1.00 AC: 1 AN: 1

Gnomad4 NFE AF: 1.00 AC: 0.99975 AN: 0.99975

Gnomad4 OTH AF: 0.985 AC: 0.984848 AN: 0.984848

Alfa AF: 0.961 Hom.: 33264

Bravo AF: 0.968

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 09, 2019

GeneDx

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	-0.83
CADD	Benign	0.62
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2706335; hg19: chr5-131892357;