11-67362651-A-G

Position:

• chr11-67362651-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RN7SKP239		n.67362651A>G		intragenic_variant
LOC100130987	NR_024469.1	n.424-24884A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000256514	ENST00000543494.1	c.17-9574T>C		intron_variant		3		ENSP00000480527.1
RN7SKP239	ENST00000364814.1	n.238A>G		non_coding_transcript_exon_variant	1/1	6
RAD9A	ENST00000622583.4	n.392-24884A>G		intron_variant		2

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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0657

Gnomad4 OTH AF: 0.221

Alfa AF: 0.106 Hom.: 3284

Bravo AF: 0.315

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Other links and lift over

dbSNP: rs1790740; hg19: chr11-67130122;