chr2-46701027-C-G

Variant names:

• chr2-46701027-C-G
• rs6737848
• NM_144949.3:c.-13+1578C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144949.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS5	NM_144949.3	MANE Select	c.-13+1578C>G		intron	N/A	NP_659198.1
	SOCS5	NM_014011.5		c.-13+1916C>G		intron	N/A	NP_054730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS5	ENST00000394861.3	TSL:1 MANE Select	c.-13+1578C>G		intron	N/A	ENSP00000378330.2
	SOCS5	ENST00000306503.5	TSL:1	c.-13+1916C>G		intron	N/A	ENSP00000305133.5
	LINC01118	ENST00000650611.2		n.172+1916C>G		intron	N/A

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

African (AFR) AF: 0.184 AC: 7624 AN: 41508

American (AMR) AF: 0.197 AC: 3015 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2176 AN: 5174

South Asian (SAS) AF: 0.295 AC: 1423 AN: 4822

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10582

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5115 AN: 67992

Other (OTH) AF: 0.140 AC: 296 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6737848; hg19: chr2-46928166;