chr14-55031230-G-A

Variant names:

• chr14-55031230-G-A
• rs1952438
• NM_199421.2:c.-219-633G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199421.2(SOCS4):​c.-219-633G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,084 control chromosomes in the GnomAD database, including 1,768 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 (1768 hom., cov: 33)
• Consequence: SOCS4 NM_199421.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 8 publications found

Genes affected

SOCS4 (HGNC:19392): (suppressor of cytokine signaling 4) 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), also known as STAT-induced STAT inhibitor (SSI), protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

SOCS4 Gene-Disease associations (from GenCC):

• autoimmune disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOCS4	NM_199421.2	c.-219-633G>A		intron_variant	Intron 1 of 2	ENST00000555846.2	NP_955453.1
SOCS4	NM_080867.3	c.-91+3759G>A		intron_variant	Intron 1 of 1		NP_543143.1
SOCS4	XM_011536425.2	c.-278-574G>A		intron_variant	Intron 1 of 2		XP_011534727.1
SOCS4	XM_011536426.2	c.-193-659G>A		intron_variant	Intron 1 of 2		XP_011534728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS4	ENST00000555846.2	c.-219-633G>A		intron_variant	Intron 1 of 2	1	NM_199421.2	ENSP00000452522.1
SOCS4	ENST00000339298.2	c.-91+3472G>A		intron_variant	Intron 1 of 1	1		ENSP00000341327.2
SOCS4	ENST00000395472.2	c.-91+3759G>A		intron_variant	Intron 1 of 1	1		ENSP00000378855.2
SOCS4	ENST00000553735.1	n.192-659G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21886 AN: 151964 Hom.: 1766 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.144 AC: 21902 AN: 152084 Hom.: 1768 Cov.: 33 AF XY: 0.145 AC XY: 10776 AN XY: 74342

African (AFR) AF: 0.109 AC: 4516 AN: 41528

American (AMR) AF: 0.0884 AC: 1352 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3468

East Asian (EAS) AF: 0.0384 AC: 199 AN: 5188

South Asian (SAS) AF: 0.175 AC: 843 AN: 4824

European-Finnish (FIN) AF: 0.209 AC: 2206 AN: 10548

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11726 AN: 67926

Other (OTH) AF: 0.127 AC: 269 AN: 2112

Alfa AF: 0.157 Hom.: 3132

Bravo AF: 0.130

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.33
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: rs1952438; hg19: chr14-55497948;