rs6737848

chr2-46701027-C-G

Variant summary

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

The NM_144949.3(SOCS5):c.-13+1578C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,148 control chromosomes in the GnomAD database, including 2,115 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 0.14 (2115 hom., cov: 32)
• Consequence: SOCS5 NM_144949.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237

Genes affected

SOCS5 (HGNC:16852): (suppressor of cytokine signaling 5) The protein encoded by this gene contains a SH2 domain and a SOCS BOX domain. The protein thus belongs to the suppressor of cytokine signaling (SOCS) family, also known as STAT-induced STAT inhibitor (SSI) protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The specific function of this protein has not yet been determined. Two alternatively spliced transcript variants encoding an identical protein have been reported. [provided by RefSeq, Jul 2008]

LINC01118 (HGNC:49261): (long intergenic non-protein coding RNA 1118)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOCS5	NM_144949.3	c.-13+1578C>G		intron_variant		ENST00000394861.3
SOCS5	NM_014011.5	c.-13+1916C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOCS5	ENST00000394861.3	c.-13+1578C>G		intron_variant		1	NM_144949.3	P1
SOCS5	ENST00000306503.5	c.-13+1916C>G		intron_variant		1		P1
LINC01118	ENST00000650611.1	n.172+1916C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21721 AN: 152030 Hom.: 2115 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.143 AC: 21737 AN: 152148 Hom.: 2115 Cov.: 32 AF XY: 0.151 AC XY: 11222 AN XY: 74404

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0752

Gnomad4 OTH AF: 0.140

Alfa AF: 0.102 Hom.: 111

Bravo AF: 0.149

Asia WGS AF: 0.384 AC: 1334 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	12
Dann	Benign	0.71

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: rs6737848; hg19: chr2-46928166;