16-11254354-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105371082 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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	n.178+4576C>G		intron_variant	Intron 1 of 2
SOCS1	NM_003745.2	c.*489G>C		downstream_gene_variant		ENST00000332029.4	NP_003736.1

Ensembl

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

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

Gnomad4 AFR exome AF: 0.0620

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.247

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

Gnomad4 AFR AF: 0.0762

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.239

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
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs33932899; hg19: chr16-11348211;