NM_005732.4:c.3618+148T>G

Variant names:

• chr5-132638371-T-G
• rs7737470
• NM_005732.4:c.3618+148T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005732.4(RAD50):​c.3618+148T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000263 in 760,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 20 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]

ENSG00000283782 (HGNC:):

TH2LCRR (HGNC:40495): (T helper type 2 locus control region associated RNA)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005732.4. 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
	RAD50	NM_005732.4	MANE Select	c.3618+148T>G		intron	N/A	NP_005723.2
	TH2LCRR	NR_132124.1		n.46-106A>C		intron	N/A
	TH2LCRR	NR_132125.1		n.190-106A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	ENST00000378823.8	TSL:1 MANE Select	c.3618+148T>G		intron	N/A	ENSP00000368100.4	Q92878-1
	ENSG00000283782	ENST00000638452.2	TSL:5	c.3321+148T>G		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	TH2LCRR	ENST00000458509.1	TSL:1	n.190-106A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000263 AC: 2 AN: 760424 Hom.: 0 AF XY: 0.00000504 AC XY: 2 AN XY: 397070

African (AFR) AF: 0.00 AC: 0 AN: 19184

American (AMR) AF: 0.0000293 AC: 1 AN: 34176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20940

East Asian (EAS) AF: 0.00 AC: 0 AN: 32792

South Asian (SAS) AF: 0.00 AC: 0 AN: 65516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2866

European-Non Finnish (NFE) AF: 0.00000196 AC: 1 AN: 510032

Other (OTH) AF: 0.00 AC: 0 AN: 36922

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		0.12

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: rs7737470; hg19: chr5-131974063;