Genetic Variant ENST00000572173.1:c.-515-13787G>T (chr16-11281429-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000572173.1(RMI2):c.-515-13787G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 644,152 control chromosomes in the GnomAD database, including 18,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3926 hom., cov: 33)

Exomes 𝑓: 0.24 ( 15000 hom. )

Consequence

RMI2
ENST00000572173.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.956

Publications

20 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:

PRM1 (HGNC:9447): (protamine 1) Predicted to enable DNA binding activity. Predicted to be involved in DNA packaging. Predicted to act upstream of or within nucleus organization and spermatid development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PRM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-11281429-G-T is Benign according to our data. Variant chr16-11281429-G-T is described in ClinVar as Benign. ClinVar VariationId is 1223123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371082	XR_933070.4 link	n.178+31651G>T		intron_variant	Intron 1 of 2
PRM1	NM_002761.3 link	c.-191C>A		upstream_gene_variant		ENST00000312511.4	NP_002752.1	P04553Q3MN80

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RMI2	ENST00000572173.1 link	c.-515-13787G>T	intron_variant	Intron 1 of 4	1		ENSP00000461206.1	Q96E14-2
RMI2	ENST00000573910.1 link	n.160+31651G>T	intron_variant	Intron 1 of 1	3
RMI2	ENST00000649869.1 link	n.152+31651G>T	intron_variant	Intron 1 of 2
PRM1	ENST00000312511.4 link	c.-191C>A	upstream_gene_variant		1	NM_002761.3	ENSP00000310515.3	P04553

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32640

AN:

152042

Hom.:

3928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.252

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.239

AC:

117650

AN:

491992

Hom.:

15000

AF XY:

0.237

AC XY:

62048

AN XY:

261816

show subpopulations

African (AFR)

AF:

0.120

AC:

1736

AN:

14500

American (AMR)

AF:

0.140

AC:

4294

AN:

30680

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

3414

AN:

16758

East Asian (EAS)

AF:

0.240

AC:

7319

AN:

30476

South Asian (SAS)

AF:

0.171

AC:

9499

AN:

55478

European-Finnish (FIN)

AF:

0.306

AC:

9297

AN:

30370

Middle Eastern (MID)

AF:

0.233

AC:

500

AN:

2148

European-Non Finnish (NFE)

AF:

0.264

AC:

74921

AN:

284258

Other (OTH)

AF:

0.244

AC:

6670

AN:

27324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4750

9500

14251

19001

23751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.214

AC:

32627

AN:

152160

Hom.:

3926

Cov.:

AF XY:

0.214

AC XY:

15910

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.116

AC:

4820

AN:

41530

American (AMR)

AF:

0.185

AC:

2834

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3466

East Asian (EAS)

AF:

0.263

AC:

1356

AN:

5162

South Asian (SAS)

AF:

0.170

AC:

819

AN:

4824

European-Finnish (FIN)

AF:

0.307

AC:

3255

AN:

10588

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.265

AC:

18003

AN:

67976

Other (OTH)

AF:

0.230

AC:

487

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1292

2584

3876

5168

6460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.247

Hom.:

1226

Bravo

AF:

0.200

Asia WGS

AF:

0.202

AC:

699

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27216534, 18390561) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.066

(source)

DANN

Benign

0.52

PhyloP100

-0.96

PromoterAI

-0.070

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over