11-67362651-A-G

Variant names:

• chr11-67362651-A-G
• rs1790740
• ENST00000543494.1:c.17-9574T>C

Variant summary

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

The ENST00000543494.1(ENSG00000256514):​c.17-9574T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,228 control chromosomes in the GnomAD database, including 11,693 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 (11693 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000256514 ENST00000543494.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 9 publications found

Genes affected

ENSG00000256514 (HGNC:):

RN7SKP239 (HGNC:45963): (RN7SK pseudogene 239)

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000543494.1. 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
	LOC100130987	NR_024469.1		n.424-24884A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000256514	ENST00000543494.1	TSL:3	c.17-9574T>C		intron	N/A	ENSP00000480527.1	A0A087WWV3
	RN7SKP239	ENST00000364814.1	TSL:6	n.238A>G		non_coding_transcript_exon	Exon 1 of 1
	RAD9A	ENST00000622583.4	TSL:2	n.392-24884A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41751 AN: 152110 Hom.: 11649 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0658

Gnomad OTH AF: 0.222

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 36 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.275 AC: 41858 AN: 152228 Hom.: 11693 Cov.: 32 AF XY: 0.273 AC XY: 20287 AN XY: 74436

African (AFR) AF: 0.704 AC: 29205 AN: 41502

American (AMR) AF: 0.311 AC: 4765 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3472

East Asian (EAS) AF: 0.233 AC: 1207 AN: 5180

South Asian (SAS) AF: 0.0646 AC: 312 AN: 4826

European-Finnish (FIN) AF: 0.110 AC: 1166 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0657 AC: 4472 AN: 68020

Other (OTH) AF: 0.221 AC: 466 AN: 2112

Alfa AF: 0.144 Hom.: 13444

Bravo AF: 0.315

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.5
DANN	Benign	0.44
PhyloP100		0.086

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1790740; hg19: chr11-67130122; COSMIC: COSV107353661; COSMIC: COSV107353661;