14-55043566-G-A

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

2

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]

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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
SOCS4NM_199421.2 linkc.525G>A p.Gln175Gln synonymous_variant 3/3 ENST00000555846.2 NP_955453.1 Q8WXH5Q5H9R6
SOCS4NM_080867.3 linkc.525G>A p.Gln175Gln synonymous_variant 2/2 NP_543143.1 Q8WXH5Q5H9R6
SOCS4XM_011536425.2 linkc.525G>A p.Gln175Gln synonymous_variant 3/3 XP_011534727.1 Q8WXH5Q5H9R6
SOCS4XM_011536426.2 linkc.525G>A p.Gln175Gln synonymous_variant 3/3 XP_011534728.1 Q8WXH5Q5H9R6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SOCS4ENST00000555846.2 linkc.525G>A p.Gln175Gln synonymous_variant 3/31 NM_199421.2 ENSP00000452522.1 Q8WXH5
SOCS4ENST00000339298.2 linkc.525G>A p.Gln175Gln synonymous_variant 2/21 ENSP00000341327.2 Q8WXH5
SOCS4ENST00000395472.2 linkc.525G>A p.Gln175Gln synonymous_variant 2/21 ENSP00000378855.2 Q8WXH5

Frequencies

GnomAD3 genomes
AF:
0.00935
AC:
1423
AN:
152166
Hom.:
21
Cov.:
32
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.:
9
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.:
22
Cov.:
32
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.:
21
Cov.:
32
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.:
7
Bravo
AF:
0.0102
Asia WGS
AF:
0.00144
AC:
5
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 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.

Other links and lift over

dbSNP: rs61734083; hg19: chr14-55510284; API