rs2069473

Variant names:

• chr5-34912252-T-C
• rs2069473
• NM_002853.4:c.308-440A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002853.4(RAD1):​c.308-440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 152,304 control chromosomes in the GnomAD database, including 314 homozygotes. 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: 𝑓 0.054 (314 hom., cov: 33)
• Consequence: RAD1 NM_002853.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 5 publications found

Genes affected

RAD1 (HGNC:9806): (RAD1 checkpoint DNA exonuclease) This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. The 9-1-1 complex is recruited by RAD17 to affected sites where it may attract specialized DNA polymerases and other DNA repair effectors. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jan 2009]

TTC23L (HGNC:26355): (tetratricopeptide repeat domain 23 like) Predicted to be located in cytoplasm; microtubule cytoskeleton; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD1	NM_002853.4	c.308-440A>G		intron_variant	Intron 3 of 5	ENST00000382038.7	NP_002844.1
RAD1	NR_026591.2	n.357-440A>G		intron_variant	Intron 2 of 4
TTC23L	NR_169875.1	n.974-6112T>C		intron_variant	Intron 7 of 15
TTC23L	NR_169876.1	n.1048-6112T>C		intron_variant	Intron 7 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD1	ENST00000382038.7	c.308-440A>G		intron_variant	Intron 3 of 5	1	NM_002853.4	ENSP00000371469.2

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8238 AN: 152186 Hom.: 314 Cov.: 33

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0541 AC: 8241 AN: 152304 Hom.: 314 Cov.: 33 AF XY: 0.0547 AC XY: 4072 AN XY: 74474

African (AFR) AF: 0.0125 AC: 518 AN: 41580

American (AMR) AF: 0.0467 AC: 715 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3470

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5182

South Asian (SAS) AF: 0.114 AC: 552 AN: 4830

European-Finnish (FIN) AF: 0.0687 AC: 729 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0739 AC: 5026 AN: 68012

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0720 Hom.: 244

Bravo AF: 0.0498

Asia WGS AF: 0.0660 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		-0.45
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: rs2069473; hg19: chr5-34912357;