14-55043616-A-G

Position:

chr14-55043616-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_199421.2(SOCS4):c.575A>G(p.Asn192Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,614,190 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

SOCS4
NM_199421.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008286536).

BP6

Variant 14-55043616-A-G is Benign according to our data. Variant chr14-55043616-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2209545.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS4	NM_199421.2 linkuse as main transcript	c.575A>G	p.Asn192Ser	missense_variant	3/3	ENST00000555846.2	NP_955453.1	Q8WXH5Q5H9R6
SOCS4	NM_080867.3 linkuse as main transcript	c.575A>G	p.Asn192Ser	missense_variant	2/2		NP_543143.1	Q8WXH5Q5H9R6
SOCS4	XM_011536425.2 linkuse as main transcript	c.575A>G	p.Asn192Ser	missense_variant	3/3		XP_011534727.1	Q8WXH5Q5H9R6
SOCS4	XM_011536426.2 linkuse as main transcript	c.575A>G	p.Asn192Ser	missense_variant	3/3		XP_011534728.1	Q8WXH5Q5H9R6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SOCS4	ENST00000555846.2 linkuse as main transcript	c.575A>G	p.Asn192Ser	missense_variant	3/3	1	NM_199421.2	ENSP00000452522.1	Q8WXH5
SOCS4	ENST00000339298.2 linkuse as main transcript	c.575A>G	p.Asn192Ser	missense_variant	2/2	1		ENSP00000341327.2	Q8WXH5
SOCS4	ENST00000395472.2 linkuse as main transcript	c.575A>G	p.Asn192Ser	missense_variant	2/2	1		ENSP00000378855.2	Q8WXH5

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000493

AC:

124

AN:

251308

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000827

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00105

AC:

1533

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000958

AC XY:

697

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.000584

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000661

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000502

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0030

DANN

Benign

0.39

DEOGEN2

Benign

0.20

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.65

.;.;T

M_CAP

Benign

0.00087

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.24

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.44

T;T;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.021

MVP

0.26

MPC

0.094

ClinPred

0.0072

GERP RS

-11

Varity_R

0.020

gMVP

0.13

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