rs4526098

Variant names:

• chr5-132557287-G-A
• rs4526098
• ENST00000533482.5:n.-38G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132557287-G-A
• chr5-132557287-G-C
• chr5-132557287-G-T

Variant summary

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

The ENST00000533482.5(RAD50):​n.-38G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,611,840 control chromosomes in the GnomAD database, including 783,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.93 (66617 hom., cov: 34)
  • Exomes 𝑓: 0.99 (716992 hom.)
• Consequence: RAD50 ENST00000533482.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 29 publications found

Genes affected

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]

RAD50 Gene-Disease associations (from GenCC):

• Nijmegen breakage syndrome-like disorder

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000283782 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-132557287-G-A is Benign according to our data. Variant chr5-132557287-G-A is described in ClinVar as [Benign]. Clinvar id is 4077036.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.-38G>A		5_prime_UTR_variant	Exon 1 of 25	ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.-38G>A		5_prime_UTR_variant	Exon 1 of 25	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2	c.-168-1997G>A		intron_variant	Intron 3 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141497 AN: 152178 Hom.: 66576 Cov.: 34

Gnomad AFR AF: 0.762

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.988

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.948

GnomAD2 exomes AF: 0.979 AC: 246201 AN: 251458 AF XY: 0.984

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.997

Gnomad OTH exome AF: 0.990

GnomAD4 exome AF: 0.990 AC: 1445590 AN: 1459544 Hom.: 716992 Cov.: 46 AF XY: 0.991 AC XY: 719847 AN XY: 726220

African (AFR) AF: 0.751 AC: 25095 AN: 33394

American (AMR) AF: 0.983 AC: 43963 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 26084 AN: 26120

East Asian (EAS) AF: 1.00 AC: 39685 AN: 39688

South Asian (SAS) AF: 0.992 AC: 85490 AN: 86206

European-Finnish (FIN) AF: 1.00 AC: 53400 AN: 53408

Middle Eastern (MID) AF: 0.970 AC: 5589 AN: 5762

European-Non Finnish (NFE) AF: 0.997 AC: 1107112 AN: 1109920

Other (OTH) AF: 0.981 AC: 59172 AN: 60332

GnomAD4 genome AF: 0.930 AC: 141591 AN: 152296 Hom.: 66617 Cov.: 34 AF XY: 0.932 AC XY: 69401 AN XY: 74470

African (AFR) AF: 0.762 AC: 31657 AN: 41520

American (AMR) AF: 0.972 AC: 14877 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3463 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5183 AN: 5184

South Asian (SAS) AF: 0.988 AC: 4773 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67808 AN: 68034

Other (OTH) AF: 0.948 AC: 2007 AN: 2116

Alfa AF: 0.974 Hom.: 53604

Bravo AF: 0.918

Asia WGS AF: 0.979 AC: 3404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		2.3
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs4526098; hg19: chr5-131892979; COSMIC: COSV99528532;