Variant 14-55043566-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_199421.2(SOCS4):c.525G>A(p.Gln175Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,614,122 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 21 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 22 hom. )

Consequence

SOCS4
NM_199421.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.821

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 14-55043566-G-A is Benign according to our data. Variant chr14-55043566-G-A is described in ClinVar as [Benign]. Clinvar id is 730044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.821 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00939 (1430/152284) while in subpopulation AFR AF= 0.0331 (1377/41560). AF 95% confidence interval is 0.0317. There are 21 homozygotes in gnomad4. There are 669 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS4	NM_199421.2 link	c.525G>A	p.Gln175Gln	synonymous_variant	3/3	ENST00000555846.2	NP_955453.1	Q8WXH5Q5H9R6
SOCS4	NM_080867.3 link	c.525G>A	p.Gln175Gln	synonymous_variant	2/2		NP_543143.1	Q8WXH5Q5H9R6
SOCS4	XM_011536425.2 link	c.525G>A	p.Gln175Gln	synonymous_variant	3/3		XP_011534727.1	Q8WXH5Q5H9R6
SOCS4	XM_011536426.2 link	c.525G>A	p.Gln175Gln	synonymous_variant	3/3		XP_011534728.1	Q8WXH5Q5H9R6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SOCS4	ENST00000555846.2 link	c.525G>A	p.Gln175Gln	synonymous_variant	3/3	1	NM_199421.2	ENSP00000452522.1	Q8WXH5
SOCS4	ENST00000339298.2 link	c.525G>A	p.Gln175Gln	synonymous_variant	2/2	1		ENSP00000341327.2	Q8WXH5
SOCS4	ENST00000395472.2 link	c.525G>A	p.Gln175Gln	synonymous_variant	2/2	1		ENSP00000378855.2	Q8WXH5

Frequencies

GnomAD3 genomes

AF:

0.00935

AC:

1423

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00235

AC:

590

AN:

251266

Hom.:

AF XY:

0.00161

AC XY:

219

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0327

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000986

AC:

1441

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000831

AC XY:

604

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0356

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000638

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00939

AC:

1430

AN:

152284

Hom.:

Cov.:

AF XY:

0.00898

AC XY:

669

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0331

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.13

DANN

Benign

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over