16-11259447-A-G

Variant names:

• chr16-11259447-A-G
• rs243327
• ENST00000572173.1:c.-516+9669A>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+9669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,972 control chromosomes in the GnomAD database, including 21,183 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 (21183 hom., cov: 32)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 39 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572173.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMI2	ENST00000572173.1	TSL:1	c.-516+9669A>G		intron	N/A	ENSP00000461206.1	Q96E14-2
	RMI2	ENST00000573910.1	TSL:3	n.160+9669A>G		intron	N/A
	RMI2	ENST00000649869.1		n.152+9669A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79141 AN: 151854 Hom.: 21125 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.522 AC: 79261 AN: 151972 Hom.: 21183 Cov.: 32 AF XY: 0.528 AC XY: 39190 AN XY: 74282

African (AFR) AF: 0.537 AC: 22257 AN: 41444

American (AMR) AF: 0.621 AC: 9485 AN: 15280

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

East Asian (EAS) AF: 0.732 AC: 3774 AN: 5156

South Asian (SAS) AF: 0.684 AC: 3290 AN: 4810

European-Finnish (FIN) AF: 0.452 AC: 4771 AN: 10554

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

European-Non Finnish (NFE) AF: 0.472 AC: 32045 AN: 67944

Other (OTH) AF: 0.517 AC: 1088 AN: 2106

Alfa AF: 0.532 Hom.: 5607

Bravo AF: 0.538

Asia WGS AF: 0.684 AC: 2379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.38
PhyloP100		-0.28
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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: rs243327;

hg19: chr16-11353304;