dbSNP rs7204628: RMI2:p.Thr123Thr (chr16-11350715-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_152308.3(RMI2):c.369A>C(p.Thr123Thr) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.458

Publications

19 publications found

Variant links:

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]

RMI2 links:

LOC105371082 (HGNC:):

LOC105371082 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RMI2	NM_152308.3 link	c.369A>C	p.Thr123Thr	synonymous_variant	Exon 2 of 2	ENST00000312499.6	NP_689521.1	Q96E14-1
RMI2	NR_130754.2 link	n.159A>C		non_coding_transcript_exon_variant	Exon 2 of 2
LOC105371082	XR_933070.4 link	n.179-29107A>C		intron_variant	Intron 1 of 2
LOC105371082	XR_933073.3 link	n.810-29107A>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMI2	ENST00000312499.6 link	c.369A>C	p.Thr123Thr	synonymous_variant	Exon 2 of 2	1	NM_152308.3	ENSP00000310356.5		Q96E14-1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34111

AN:

152050

Hom.:

4003

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.196

AC:

49136

AN:

250918

AF XY:

0.199

show subpopulations

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 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.:

AF XY:

0.236

AC XY:

171155

AN XY:

726566

show subpopulations

African (AFR)

AF:

0.234

AC:

7819

AN:

33422

American (AMR)

AF:

0.135

AC:

6052

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

4722

AN:

26102

East Asian (EAS)

AF:

0.00375

AC:

149

AN:

39692

South Asian (SAS)

AF:

0.178

AC:

15336

AN:

86144

European-Finnish (FIN)

AF:

0.240

AC:

12795

AN:

53396

Middle Eastern (MID)

AF:

0.186

AC:

1070

AN:

5766

European-Non Finnish (NFE)

AF:

0.258

AC:

286741

AN:

1110924

Other (OTH)

AF:

0.228

AC:

13775

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

12765

25530

38295

51060

63825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9696

19392

29088

38784

48480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.224

AC:

34114

AN:

152168

Hom.:

4006

Cov.:

AF XY:

0.221

AC XY:

16437

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.239

AC:

9930

AN:

41492

American (AMR)

AF:

0.185

AC:

2832

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3472

East Asian (EAS)

AF:

0.00829

AC:

AN:

5188

South Asian (SAS)

AF:

0.175

AC:

844

AN:

4824

European-Finnish (FIN)

AF:

0.231

AC:

2441

AN:

10582

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16600

AN:

67992

Other (OTH)

AF:

0.227

AC:

479

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1334

2667

4001

5334

6668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.212

Hom.:

2624

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

(source)

DANN

Benign

0.82

PhyloP100

-0.46

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over