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1-153543831-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002961.3(S100A4):c.234C>T(p.Phe78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,188 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 33 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 27 hom. )

Consequence

S100A4
NM_002961.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.90
Variant links:
Genes affected
S100A4 (HGNC:10494): (S100 calcium binding protein A4) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-153543831-G-A is Benign according to our data. Variant chr1-153543831-G-A is described in ClinVar as [Benign]. Clinvar id is 777935.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.9 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1720/152316) while in subpopulation AFR AF= 0.0392 (1627/41552). AF 95% confidence interval is 0.0376. There are 33 homozygotes in gnomad4. There are 808 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 32 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A4NM_002961.3 linkuse as main transcriptc.234C>T p.Phe78= synonymous_variant 3/3 ENST00000368716.9
S100A4NM_019554.3 linkuse as main transcriptc.234C>T p.Phe78= synonymous_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A4ENST00000368716.9 linkuse as main transcriptc.234C>T p.Phe78= synonymous_variant 3/31 NM_002961.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0112
AC:
1712
AN:
152198
Hom.:
32
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0391
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00451
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00284
AC:
714
AN:
251492
Hom.:
16
AF XY:
0.00188
AC XY:
256
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.0396
Gnomad AMR exome
AF:
0.00159
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000527
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00111
AC:
1628
AN:
1461872
Hom.:
27
Cov.:
31
AF XY:
0.000902
AC XY:
656
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0400
Gnomad4 AMR exome
AF:
0.00195
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000360
Gnomad4 OTH exome
AF:
0.00228
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0113
AC:
1720
AN:
152316
Hom.:
33
Cov.:
32
AF XY:
0.0108
AC XY:
808
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0392
Gnomad4 AMR
AF:
0.00451
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00756
Alfa
AF:
0.00647
Hom.:
8
Bravo
AF:
0.0126
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
12
Dann
Benign
0.88

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: rs9003; hg19: chr1-153516307; API