ENST00000572173.1:c.-516+11335A>G

Variant names:

• chr16-11261113-A-G
• rs243324
• ENST00000572173.1:c.-516+11335A>G

Variant summary

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

The ENST00000572173.1(RMI2):​c.-516+11335A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,934 control chromosomes in the GnomAD database, including 20,864 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 0.52 (20864 hom., cov: 32)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 35 publications found

Genes affected

RMI2 (HGNC:28349): (RecQ mediated genome instability 2) RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]

LOC105371082 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371082	XR_933070.4	n.178+11335A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMI2	ENST00000572173.1	c.-516+11335A>G		intron_variant	Intron 1 of 4	1		ENSP00000461206.1
RMI2	ENST00000573910.1	n.160+11335A>G		intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1	n.152+11335A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78535 AN: 151816 Hom.: 20815 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.518 AC: 78639 AN: 151934 Hom.: 20864 Cov.: 32 AF XY: 0.524 AC XY: 38893 AN XY: 74260

African (AFR) AF: 0.524 AC: 21703 AN: 41406

American (AMR) AF: 0.619 AC: 9455 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2049 AN: 3472

East Asian (EAS) AF: 0.732 AC: 3770 AN: 5150

South Asian (SAS) AF: 0.684 AC: 3297 AN: 4818

European-Finnish (FIN) AF: 0.451 AC: 4766 AN: 10562

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32024 AN: 67938

Other (OTH) AF: 0.510 AC: 1077 AN: 2110

Alfa AF: 0.498 Hom.: 58250

Bravo AF: 0.534

Asia WGS AF: 0.680 AC: 2363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.5
DANN	Benign	0.30
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs243324; hg19: chr16-11354970; COSMIC: COSV59661279; COSMIC: COSV59661279;