rs497184

Variant names:

• chr16-11295732-G-A
• rs497184
• ENST00000572173.1:c.-437+438G>A

Variant summary

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

The ENST00000572173.1(RMI2):​c.-437+438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,056 control chromosomes in the GnomAD database, including 1,738 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 0.15 (1738 hom., cov: 32)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.670
• Publications: 5 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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371082	XR_933070.4	n.178+45954G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMI2	ENST00000572173.1	c.-437+438G>A		intron_variant	Intron 2 of 4	1		ENSP00000461206.1
RMI2	ENST00000573910.1	n.161-20720G>A		intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1	n.152+45954G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22085 AN: 151938 Hom.: 1737 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0462

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.145 AC: 22091 AN: 152056 Hom.: 1738 Cov.: 32 AF XY: 0.140 AC XY: 10438 AN XY: 74316

African (AFR) AF: 0.0989 AC: 4104 AN: 41476

American (AMR) AF: 0.105 AC: 1610 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3472

East Asian (EAS) AF: 0.0463 AC: 240 AN: 5178

South Asian (SAS) AF: 0.117 AC: 565 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10556

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13050 AN: 67966

Other (OTH) AF: 0.122 AC: 257 AN: 2102

Alfa AF: 0.176 Hom.: 494

Bravo AF: 0.141

Asia WGS AF: 0.0760 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.82
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: rs497184; hg19: chr16-11389589;