ENST00000572173.1:c.-437+6764G>A

Variant names:

• chr16-11302058-G-A
• rs12599908
• ENST00000572173.1:c.-437+6764G>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+6764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,090 control chromosomes in the GnomAD database, including 1,888 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 (1888 hom., cov: 32)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 7 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=-0.93).
• 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+52280G>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+6764G>A		intron_variant	Intron 2 of 4	1		ENSP00000461206.1
RMI2	ENST00000573910.1	n.161-14394G>A		intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1	n.152+52280G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23488 AN: 151972 Hom.: 1887 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.155 AC: 23505 AN: 152090 Hom.: 1888 Cov.: 32 AF XY: 0.150 AC XY: 11119 AN XY: 74336

African (AFR) AF: 0.132 AC: 5482 AN: 41474

American (AMR) AF: 0.108 AC: 1644 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3466

East Asian (EAS) AF: 0.0445 AC: 231 AN: 5186

South Asian (SAS) AF: 0.116 AC: 558 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1579 AN: 10562

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

European-Non Finnish (NFE) AF: 0.192 AC: 13052 AN: 68000

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.100 Hom.: 142

Bravo AF: 0.152

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.35
PhyloP100		-0.51
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: rs12599908; hg19: chr16-11395915;