11-67357752-T-C

Variant names:

• chr11-67357752-T-C
• rs1638567
• ENST00000543494.1:c.17-4675A>G

Variant summary

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

The ENST00000543494.1(ENSG00000256514):​c.17-4675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,100 control chromosomes in the GnomAD database, including 11,639 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 0.27 (11639 hom., cov: 32)
• Consequence: ENSG00000256514 ENST00000543494.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 12 publications found

Genes affected

ENSG00000256514 (HGNC:):

RAD9A (HGNC:9827): (RAD9 checkpoint clamp component A) This gene product is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair. This protein possesses 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. It forms a checkpoint protein complex with RAD1 and HUS1. This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100130987	NR_024469.1	n.424-29783T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000256514	ENST00000543494.1	c.17-4675A>G		intron_variant	Intron 1 of 3	3		ENSP00000480527.1
RAD9A	ENST00000622583.4	n.392-29783T>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41644 AN: 151982 Hom.: 11597 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.0540

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0658

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.274 AC: 41749 AN: 152100 Hom.: 11639 Cov.: 32 AF XY: 0.272 AC XY: 20225 AN XY: 74368

African (AFR) AF: 0.703 AC: 29126 AN: 41448

American (AMR) AF: 0.311 AC: 4753 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0540 AC: 187 AN: 3464

East Asian (EAS) AF: 0.233 AC: 1199 AN: 5156

South Asian (SAS) AF: 0.0642 AC: 310 AN: 4826

European-Finnish (FIN) AF: 0.109 AC: 1161 AN: 10604

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0658 AC: 4476 AN: 68004

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.129 Hom.: 5699

Bravo AF: 0.315

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.84
PhyloP100		-1.0

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: rs1638567; hg19: chr11-67125223;