rs33977706

Variant names:

• chr16-11256298-C-A
• rs33977706
• ENST00000572173.1:c.-516+6520C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-11256298-C-A
• chr16-11256298-C-G
• chr16-11256298-C-T

Variant summary

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

The ENST00000572173.1(RMI2):​c.-516+6520C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,236 control chromosomes in the GnomAD database, including 4,199 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 0.21 (4175 hom., cov: 32)
  • Exomes 𝑓: 0.28 (24 hom.)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 21 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 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.-270G>T		upstream_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+6520C>A		intron	N/A	ENSP00000461206.1	Q96E14-2
	SOCS1	ENST00000858080.1		c.-51+107G>T		intron	N/A	ENSP00000528139.1
	RMI2	ENST00000573910.1	TSL:3	n.160+6520C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32206 AN: 151750 Hom.: 4177 Cov.: 32

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.278 AC: 104 AN: 374 Hom.: 24 AF XY: 0.293 AC XY: 79 AN XY: 270

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.389 AC: 7 AN: 18

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.275 AC: 88 AN: 320

Other (OTH) AF: 0.400 AC: 4 AN: 10

GnomAD4 genome AF: 0.212 AC: 32185 AN: 151862 Hom.: 4175 Cov.: 32 AF XY: 0.211 AC XY: 15686 AN XY: 74228

African (AFR) AF: 0.0680 AC: 2824 AN: 41518

American (AMR) AF: 0.190 AC: 2906 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1296 AN: 5106

South Asian (SAS) AF: 0.172 AC: 830 AN: 4824

European-Finnish (FIN) AF: 0.320 AC: 3385 AN: 10562

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19214 AN: 67790

Other (OTH) AF: 0.233 AC: 491 AN: 2104

Alfa AF: 0.213 Hom.: 1532

Bravo AF: 0.195

Asia WGS AF: 0.192 AC: 664 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.6
DANN	Benign	0.82
PhyloP100		0.34
PromoterAI		-0.033	Neutral
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: rs33977706;

hg19: chr16-11350155;