16-11253191-T-C

Variant names:

• chr16-11253191-T-C
• rs1111186
• ENST00000572173.1:c.-516+3413T>C

Variant summary

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

The ENST00000572173.1(RMI2):​c.-516+3413T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,244 control chromosomes in the GnomAD database, including 11,872 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 0.38 (11872 hom., cov: 29)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371082	XR_933070.4	n.178+3413T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMI2	ENST00000572173.1	c.-516+3413T>C		intron_variant	Intron 1 of 4	1		ENSP00000461206.1
RMI2	ENST00000573910.1	n.160+3413T>C		intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1	n.152+3413T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57141 AN: 151128 Hom.: 11835 Cov.: 29

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.378 AC: 57232 AN: 151244 Hom.: 11872 Cov.: 29 AF XY: 0.389 AC XY: 28746 AN XY: 73860

African (AFR) AF: 0.399 AC: 16416 AN: 41092

American (AMR) AF: 0.528 AC: 8035 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3466

East Asian (EAS) AF: 0.733 AC: 3778 AN: 5154

South Asian (SAS) AF: 0.587 AC: 2809 AN: 4788

European-Finnish (FIN) AF: 0.313 AC: 3247 AN: 10384

Middle Eastern (MID) AF: 0.399 AC: 115 AN: 288

European-Non Finnish (NFE) AF: 0.301 AC: 20414 AN: 67850

Other (OTH) AF: 0.388 AC: 814 AN: 2100

Alfa AF: 0.362 Hom.: 1520

Bravo AF: 0.401

Asia WGS AF: 0.620 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.63
PhyloP100		-0.17
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: rs1111186; hg19: chr16-11347048;