14-55031230-G-A

Position:

• chr14-55031230-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SOCS4	NM_199421.2	c.-219-633G>A		intron_variant		ENST00000555846.2	NP_955453.1
SOCS4	NM_080867.3	c.-91+3759G>A		intron_variant			NP_543143.1
SOCS4	XM_011536425.2	c.-278-574G>A		intron_variant			XP_011534727.1
SOCS4	XM_011536426.2	c.-193-659G>A		intron_variant			XP_011534728.1

Ensembl

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0384

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.127

Alfa AF: 0.159 Hom.: 2200

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

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: rs1952438; hg19: chr14-55497948;