Genetic Variant ENST00000572173.1:c.-516+4576C>G (chr16-11254354-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000572173.1(RMI2):c.-516+4576C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 202,332 control chromosomes in the GnomAD database, including 6,248 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 ( 4546 hom., cov: 32)

Exomes 𝑓: 0.25 ( 1702 hom. )

Consequence

RMI2
ENST00000572173.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00100

Publications

15 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:

SOCS1 (HGNC:19383): (suppressor of cytokine signaling 1) This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), CSF2/GM-CSF, and interferon (IFN)-gamma. The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-gamma action, which is required for normal postnatal growth and survival. [provided by RefSeq, Jul 2008]

SOCS1 Gene-Disease associations (from GenCC):

autoinflammatory syndrome with immunodeficiency
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autoimmune disease
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SOCS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371082	XR_933070.4 link	n.178+4576C>G		intron_variant	Intron 1 of 2
SOCS1	NM_003745.2 link	c.*489G>C		downstream_gene_variant		ENST00000332029.4	NP_003736.1	O15524Q4JHT5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS1	ENST00000332029.4 link	c.*489G>C		downstream_gene_variant		1	NM_003745.2	ENSP00000329418.2		O15524

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33750

AN:

151946

Hom.:

4548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0763

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.246

AC:

12378

AN:

50268

Hom.:

1702

AF XY:

0.250

AC XY:

5893

AN XY:

23576

show subpopulations

African (AFR)

AF:

0.0620

AC:

131

AN:

2114

American (AMR)

AF:

0.160

AC:

227

AN:

1420

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

666

AN:

3076

East Asian (EAS)

AF:

0.193

AC:

1597

AN:

8268

South Asian (SAS)

AF:

0.139

AC:

AN:

416

European-Finnish (FIN)

AF:

0.232

AC:

AN:

112

Middle Eastern (MID)

AF:

0.196

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.282

AC:

8590

AN:

30410

Other (OTH)

AF:

0.247

AC:

1022

AN:

4140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

428

855

1283

1710

2138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.222

AC:

33735

AN:

152064

Hom.:

4546

Cov.:

AF XY:

0.221

AC XY:

16444

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0762

AC:

3160

AN:

41492

American (AMR)

AF:

0.192

AC:

2930

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

760

AN:

3472

East Asian (EAS)

AF:

0.253

AC:

1308

AN:

5176

South Asian (SAS)

AF:

0.174

AC:

842

AN:

4826

European-Finnish (FIN)

AF:

0.337

AC:

3550

AN:

10528

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.297

AC:

20196

AN:

67976

Other (OTH)

AF:

0.239

AC:

504

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1302

2603

3905

5206

6508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.150

Hom.:

335

Bravo

AF:

0.203

Asia WGS

AF:

0.198

AC:

686

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.7

(source)

DANN

Benign

0.45

PhyloP100

-0.0010

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

Computational scores

Splicing

Publications

Other links and lift over