rs12596260

Variant names:

• chr16-11304408-T-G
• rs12596260
• ENST00000572173.1:c.-436-8421T>G

Variant summary

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

The ENST00000572173.1(RMI2):​c.-436-8421T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,078 control chromosomes in the GnomAD database, including 1,740 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 (1740 hom., cov: 30)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 6 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=-0.87).
• 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+54630T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMI2	ENST00000572173.1	c.-436-8421T>G		intron_variant	Intron 2 of 4	1		ENSP00000461206.1
RMI2	ENST00000573910.1	n.161-12044T>G		intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1	n.152+54630T>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22122 AN: 151960 Hom.: 1739 Cov.: 30

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0455

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.146 AC: 22130 AN: 152078 Hom.: 1740 Cov.: 30 AF XY: 0.141 AC XY: 10468 AN XY: 74342

African (AFR) AF: 0.0998 AC: 4140 AN: 41496

American (AMR) AF: 0.104 AC: 1595 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3466

East Asian (EAS) AF: 0.0456 AC: 236 AN: 5172

South Asian (SAS) AF: 0.116 AC: 558 AN: 4814

European-Finnish (FIN) AF: 0.149 AC: 1580 AN: 10580

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

European-Non Finnish (NFE) AF: 0.192 AC: 13065 AN: 67970

Other (OTH) AF: 0.121 AC: 256 AN: 2110

Alfa AF: 0.178 Hom.: 1575

Bravo AF: 0.142

Asia WGS AF: 0.0740 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Benign	0.78
PhyloP100		1.1
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: rs12596260; hg19: chr16-11398265;