rs7737470

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-132638371-T-A
• chr5-132638371-T-G

Variant summary

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

The NM_005732.4(RAD50):​c.3618+148T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 911,576 control chromosomes in the GnomAD database, including 21,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3897 hom., cov: 32)
  • Exomes 𝑓: 0.21 (17288 hom.)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-132638371-T-A is Benign according to our data. Variant chr5-132638371-T-A is described in ClinVar as Benign. ClinVar VariationId is 1269272.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

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>A		intron	N/A	NP_005723.2
	TH2LCRR	NR_132124.1		n.46-106A>T		intron	N/A
	TH2LCRR	NR_132125.1		n.190-106A>T		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>A		intron	N/A	ENSP00000368100.4	Q92878-1
	ENSG00000283782	ENST00000638452.2	TSL:5	c.3321+148T>A		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	TH2LCRR	ENST00000458509.1	TSL:1	n.190-106A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33761 AN: 152020 Hom.: 3878 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.209 AC: 158636 AN: 759438 Hom.: 17288 AF XY: 0.212 AC XY: 83897 AN XY: 396576

African (AFR) AF: 0.245 AC: 4700 AN: 19164

American (AMR) AF: 0.159 AC: 5425 AN: 34150

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 4780 AN: 20928

East Asian (EAS) AF: 0.200 AC: 6545 AN: 32770

South Asian (SAS) AF: 0.237 AC: 15508 AN: 65490

European-Finnish (FIN) AF: 0.251 AC: 9533 AN: 37938

Middle Eastern (MID) AF: 0.222 AC: 635 AN: 2864

European-Non Finnish (NFE) AF: 0.204 AC: 103989 AN: 509262

Other (OTH) AF: 0.204 AC: 7521 AN: 36872

GnomAD4 genome AF: 0.222 AC: 33818 AN: 152138 Hom.: 3897 Cov.: 32 AF XY: 0.223 AC XY: 16578 AN XY: 74382

African (AFR) AF: 0.254 AC: 10551 AN: 41496

American (AMR) AF: 0.167 AC: 2560 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3472

East Asian (EAS) AF: 0.178 AC: 920 AN: 5180

South Asian (SAS) AF: 0.233 AC: 1122 AN: 4820

European-Finnish (FIN) AF: 0.244 AC: 2579 AN: 10588

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14663 AN: 67978

Other (OTH) AF: 0.213 AC: 448 AN: 2104

Alfa AF: 0.147 Hom.: 287

Bravo AF: 0.215

Asia WGS AF: 0.204 AC: 712 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	-0.85
CADD	Benign	2.2
DANN	Benign	0.53
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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;