rs7204628

chr16-11350715-A-Cchr16-11350715-A-Gchr16-11350715-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152308.3(RMI2):c.369A>C(p.Thr123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,612,614 control chromosomes in the GnomAD database, including 48,024 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 0.22 (4006 hom., cov: 33)
  • Exomes 𝑓: 0.24 (44018 hom.)
• Consequence: RMI2 NM_152308.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.458 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMI2	NM_152308.3	c.369A>C	p.Thr123=	synonymous_variant	2/2	ENST00000312499.6
LOC105371082	XR_933070.4	n.179-29107A>C		intron_variant, non_coding_transcript_variant
RMI2	NR_130754.2	n.159A>C		non_coding_transcript_exon_variant	2/2
LOC105371082	XR_933073.3	n.810-29107A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMI2	ENST00000312499.6	c.369A>C	p.Thr123=	synonymous_variant	2/2	1	NM_152308.3	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34111 AN: 152050 Hom.: 4003 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.00827

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.228

GnomAD3 exomes AF: 0.196 AC: 49136 AN: 250918 Hom.: 5560 AF XY: 0.199 AC XY: 26927 AN XY: 135638

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.00489

Gnomad SAS exome AF: 0.183

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.238

Gnomad OTH exome AF: 0.212

GnomAD4 exome AF: 0.239 AC: 348459 AN: 1460446 Hom.: 44018 Cov.: 32 AF XY: 0.236 AC XY: 171155 AN XY: 726566

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.00375

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.224 AC: 34114 AN: 152168 Hom.: 4006 Cov.: 33 AF XY: 0.221 AC XY: 16437 AN XY: 74388

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.00829

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.227

Alfa AF: 0.214 Hom.: 2030

Bravo AF: 0.219

Asia WGS AF: 0.126 AC: 442 AN: 3478

EpiCase AF: 0.240

EpiControl AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	2.4
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7204628; hg19: chr16-11444572; COSMIC: COSV56963902; COSMIC: COSV56963902;