ENST00000572173.1:c.-516+4223T>C

Variant names:

• chr16-11254001-T-C
• rs4780355
• ENST00000572173.1:c.-516+4223T>C

Variant summary

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

The ENST00000572173.1(RMI2):​c.-516+4223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 150,650 control chromosomes in the GnomAD database, including 12,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.39 (12708 hom., cov: 28)
• Consequence: RMI2 ENST00000572173.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444
• Publications: 48 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: ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMI2	ENST00000572173.1	TSL:1	c.-516+4223T>C		intron	N/A	ENSP00000461206.1	Q96E14-2
	SOCS1	ENST00000644787.2		c.*842A>G		3_prime_UTR	Exon 1 of 1	ENSP00000496577.1
	RMI2	ENST00000573910.1	TSL:3	n.160+4223T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59062 AN: 150532 Hom.: 12668 Cov.: 28

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.391

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59161 AN: 150650 Hom.: 12708 Cov.: 28 AF XY: 0.403 AC XY: 29622 AN XY: 73504

African (AFR) AF: 0.449 AC: 18347 AN: 40894

American (AMR) AF: 0.533 AC: 8051 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1334 AN: 3468

East Asian (EAS) AF: 0.734 AC: 3723 AN: 5074

South Asian (SAS) AF: 0.590 AC: 2805 AN: 4758

European-Finnish (FIN) AF: 0.317 AC: 3264 AN: 10304

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20426 AN: 67752

Other (OTH) AF: 0.394 AC: 824 AN: 2092

Alfa AF: 0.343 Hom.: 34861

Bravo AF: 0.416

Asia WGS AF: 0.624 AC: 2167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.9
DANN	Benign	0.70
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4780355; hg19: chr16-11347858;