16-11254915-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_003745.2(SOCS1):c.564C>T(p.Arg188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000684 in 1,489,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00071 (0 hom.)
• Consequence: SOCS1 NM_003745.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 16-11254915-G-A is Benign according to our data. Variant chr16-11254915-G-A is described in ClinVar as [Benign]. Clinvar id is 721574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.089 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000446 (68/152298) while in subpopulation NFE AF= 0.000603 (41/68004). AF 95% confidence interval is 0.000457. There are 0 homozygotes in gnomad4. There are 43 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 68 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOCS1	NM_003745.2	c.564C>T	p.Arg188=	synonymous_variant	2/2	ENST00000332029.4
LOC105371082	XR_933070.4	n.178+5137G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOCS1	ENST00000332029.4	c.564C>T	p.Arg188=	synonymous_variant	2/2	1	NM_003745.2	P1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000938 AC: 110 AN: 117270 Hom.: 0 AF XY: 0.000901 AC XY: 59 AN XY: 65502

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000908

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000173

Gnomad FIN exome AF: 0.00361

Gnomad NFE exome AF: 0.000870

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000711 AC: 951 AN: 1337458 Hom.: 0 Cov.: 32 AF XY: 0.000670 AC XY: 443 AN XY: 661236

Gnomad4 AFR exome AF: 0.0000378

Gnomad4 AMR exome AF: 0.000190

Gnomad4 ASJ exome AF: 0.0000497

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.00342

Gnomad4 NFE exome AF: 0.000688

Gnomad4 OTH exome AF: 0.000731

GnomAD4 genome AF: 0.000446 AC: 68 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.000577 AC XY: 43 AN XY: 74486

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000562 Hom.: 0

Bravo AF: 0.000329

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	10
Dann	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs201368715; hg19: chr16-11348772; COSMIC: COSV59658859;