chr16-11288838-C-T

Variant names:

• chr16-11288838-C-T
• rs1646026
• ENST00000572173.1:c.-515-6378C>T

Variant summary

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

The ENST00000572173.1(RMI2):​c.-515-6378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,202 control chromosomes in the GnomAD database, including 2,313 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 0.17 (2313 hom., cov: 32)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967
• Publications: 9 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 = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371082	XR_933070.4	n.178+39060C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMI2	ENST00000572173.1	c.-515-6378C>T		intron_variant	Intron 1 of 4	1		ENSP00000461206.1
RMI2	ENST00000573910.1	n.161-27614C>T		intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1	n.152+39060C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26246 AN: 152084 Hom.: 2308 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.173 AC: 26268 AN: 152202 Hom.: 2313 Cov.: 32 AF XY: 0.167 AC XY: 12443 AN XY: 74410

African (AFR) AF: 0.191 AC: 7923 AN: 41540

American (AMR) AF: 0.120 AC: 1829 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3468

East Asian (EAS) AF: 0.0472 AC: 244 AN: 5174

South Asian (SAS) AF: 0.127 AC: 613 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1586 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13085 AN: 67984

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.184 Hom.: 7432

Bravo AF: 0.172

Asia WGS AF: 0.0840 AC: 296 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	1.0
DANN	Benign	0.55
PhyloP100		-0.97
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: rs1646026; hg19: chr16-11382695;