chr5-132556665-C-T

Variant names:

• chr5-132556665-C-T
• rs2706335
• ENST00000638452.2: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
• Publications: 9 publications found

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000416135.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-168-2619C>T		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	RAD50	ENST00000416135.5	TSL:1	c.-169+192C>T		intron	N/A	ENSP00000389515.1	C9JNH8
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-169+192C>T		intron	N/A	ENSP00000491158.2	A0A1W2PQ90

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

African (AFR) AF: 0.892 AC: 18346 AN: 20558

American (AMR) AF: 0.994 AC: 16707 AN: 16812

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 14096 AN: 14096

East Asian (EAS) AF: 1.00 AC: 11536 AN: 11536

South Asian (SAS) AF: 1.00 AC: 62223 AN: 62236

European-Finnish (FIN) AF: 1.00 AC: 25904 AN: 25904

Middle Eastern (MID) AF: 0.994 AC: 4236 AN: 4260

European-Non Finnish (NFE) AF: 1.00 AC: 889481 AN: 889574

Other (OTH) 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

African (AFR) AF: 0.903 AC: 37512 AN: 41534

American (AMR) AF: 0.990 AC: 15146 AN: 15302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4826 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10630 AN: 10630

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68023 AN: 68040

Other (OTH) AF: 0.985 AC: 2080 AN: 2112

Alfa AF: 0.961 Hom.: 33264

Bravo AF: 0.968

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.62
DANN	Benign	0.61
PhyloP100		-1.9
PromoterAI		-0.039	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2706335; hg19: chr5-131892357;