rs7242186

Positions:

• chr18-70314625-G-A
• chr18-70314625-G-C
• chr18-70314625-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004232.4(SOCS6):​c.-126-9918G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,012 control chromosomes in the GnomAD database, including 42,501 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 0.74 (42501 hom., cov: 31)
• Consequence: SOCS6 NM_004232.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

Genes affected

SOCS6 (HGNC:16833): (suppressor of cytokine signaling 6) The protein encoded by this gene contains a SH2 domain and a CIS homolog domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by GM-CSF and EPO in hematopoietic cells. A high expression level of this gene was found in factor-independent chronic myelogenous leukemia (CML) and erythroleukemia (HEL) cell lines. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS6	NM_004232.4	c.-126-9918G>A		intron_variant		ENST00000397942.4	NP_004223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOCS6	ENST00000397942.4	c.-126-9918G>A		intron_variant		1	NM_004232.4	ENSP00000381034.3
SOCS6	ENST00000582322.1	c.-127+385G>A		intron_variant		3		ENSP00000463395.1
SOCS6	ENST00000578377.1	c.-126-9918G>A		intron_variant		3		ENSP00000463064.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113147 AN: 151892 Hom.: 42467 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.745 AC: 113239 AN: 152012 Hom.: 42501 Cov.: 31 AF XY: 0.749 AC XY: 55648 AN XY: 74318

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.727

Alfa AF: 0.753 Hom.: 92878

Bravo AF: 0.746

Asia WGS AF: 0.866 AC: 3008 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.36
DANN	Benign	0.32

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: rs7242186; hg19: chr18-67981861;