Variant rs7737470 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.115

Variant links:

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 links:

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

TH2LCRR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RAD50	NM_005732.4 linkuse as main transcript	c.3618+148T>A	intron_variant	ENST00000378823.8
TH2LCRR	NR_132124.1 linkuse as main transcript	n.46-106A>T	intron_variant, non_coding_transcript_variant
TH2LCRR	NR_132125.1 linkuse as main transcript	n.190-106A>T	intron_variant, non_coding_transcript_variant
TH2LCRR	NR_132126.1 linkuse as main transcript	n.175-106A>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8 linkuse as main transcript	c.3618+148T>A		intron_variant		1	NM_005732.4	P1	Q92878-1
TH2LCRR	ENST00000435042.1 linkuse as main transcript	n.283-106A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33761

AN:

152020

Hom.:

3878

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.251

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.222

AC:

33818

AN:

152138

Hom.:

3897

Cov.:

AF XY:

0.223

AC XY:

16578

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.178

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.216

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.147

Hom.:

287

Bravo

AF:

0.215

Asia WGS

AF:

0.204

AC:

712

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.2

DANN

Benign

0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over