ENST00000572173.1:c.-516+4576C>G

Variant names:

• chr16-11254354-C-G
• rs33932899
• ENST00000572173.1:c.-516+4576C>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 15 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]

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: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen
• autoimmune disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC105371082 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572173.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS1	NM_003745.2	MANE Select	c.*489G>C		downstream_gene	N/A	NP_003736.1	Q4JHT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMI2	ENST00000572173.1	TSL:1	c.-516+4576C>G		intron	N/A	ENSP00000461206.1	Q96E14-2
	SOCS1	ENST00000644787.2		c.*489G>C		3_prime_UTR	Exon 1 of 1	ENSP00000496577.1
	RMI2	ENST00000573910.1	TSL:3	n.160+4576C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33750 AN: 151946 Hom.: 4548 Cov.: 32

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

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: 58 AN: 416

European-Finnish (FIN) AF: 0.232 AC: 26 AN: 112

Middle Eastern (MID) AF: 0.196 AC: 61 AN: 312

European-Non Finnish (NFE) AF: 0.282 AC: 8590 AN: 30410

Other (OTH) AF: 0.247 AC: 1022 AN: 4140

GnomAD4 genome AF: 0.222 AC: 33735 AN: 152064 Hom.: 4546 Cov.: 32 AF XY: 0.221 AC XY: 16444 AN XY: 74328

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: 67 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20196 AN: 67976

Other (OTH) AF: 0.239 AC: 504 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.45
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs33932899;

hg19: chr16-11348211;