rs587778690

Variant names:

• chr16-11255339-G-GCCGGGA
• rs587778690
• NM_003745.2:c.134_139dupTCCCGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003745.2(SOCS1):​c.134_139dupTCCCGG​(p.Val45_Pro46dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000934 in 1,428,798 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00084 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (1 hom.)
• Consequence: SOCS1 NM_003745.2 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.350
• Publications: 3 publications found

Genes affected

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]

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:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-11255339-G-GCCGGGA is Benign according to our data. Variant chr16-11255339-G-GCCGGGA is described in ClinVar as Benign. ClinVar VariationId is 135271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000835 (127/152060) while in subpopulation AMR AF = 0.00124 (19/15288). AF 95% confidence interval is 0.000889. There are 0 homozygotes in GnomAd4. There are 63 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 127 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003745.2. 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.134_139dupTCCCGG	p.Val45_Pro46dup	conservative_inframe_insertion	Exon 2 of 2	NP_003736.1	Q4JHT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS1	ENST00000332029.4	TSL:1 MANE Select	c.134_139dupTCCCGG	p.Val45_Pro46dup	conservative_inframe_insertion	Exon 2 of 2	ENSP00000329418.2	O15524
	RMI2	ENST00000572173.1	TSL:1	c.-516+5565_-516+5570dupGGACCG		intron	N/A	ENSP00000461206.1	Q96E14-2
	SOCS1	ENST00000644787.2		c.134_139dupTCCCGG	p.Val45_Pro46dup	conservative_inframe_insertion	Exon 1 of 1	ENSP00000496577.1

Frequencies

GnomAD3 genomes AF: 0.000836 AC: 127 AN: 151952 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000285

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000291 AC: 14 AN: 48048 AF XY: 0.000244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000302

Gnomad ASJ exome AF: 0.000232

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000526

Gnomad OTH exome AF: 0.000713

GnomAD4 exome AF: 0.000946 AC: 1208 AN: 1276738 Hom.: 1 Cov.: 32 AF XY: 0.000967 AC XY: 607 AN XY: 627500

African (AFR) AF: 0.000360 AC: 9 AN: 24976

American (AMR) AF: 0.000597 AC: 10 AN: 16760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20868

East Asian (EAS) AF: 0.0000357 AC: 1 AN: 28014

South Asian (SAS) AF: 0.0000629 AC: 4 AN: 63598

European-Finnish (FIN) AF: 0.000137 AC: 5 AN: 36408

Middle Eastern (MID) AF: 0.00410 AC: 20 AN: 4882

European-Non Finnish (NFE) AF: 0.00108 AC: 1114 AN: 1028568

Other (OTH) AF: 0.000854 AC: 45 AN: 52664

GnomAD4 genome AF: 0.000835 AC: 127 AN: 152060 Hom.: 0 Cov.: 33 AF XY: 0.000847 AC XY: 63 AN XY: 74344

African (AFR) AF: 0.000650 AC: 27 AN: 41518

American (AMR) AF: 0.00124 AC: 19 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000285 AC: 3 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 67950

Other (OTH) AF: 0.00190 AC: 4 AN: 2106

Alfa AF: 0.000759 Hom.: 0

Bravo AF: 0.000846

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=72/28	polymorphism

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: rs587778690;

hg19: chr16-11349196;