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GeneBe

4-143514002-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003601.4(SMARCA5):c.78C>T(p.Ser26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,549,838 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 5 hom. )

Consequence

SMARCA5
NM_003601.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17
Variant links:
Genes affected
SMARCA5 (HGNC:11101): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The protein encoded by this gene is a component of the chromatin remodeling and spacing factor RSF, a facilitator of the transcription of class II genes by RNA polymerase II. The encoded protein is similar in sequence to the Drosophila ISWI chromatin remodeling protein. [provided by RefSeq, Jul 2008]
SMARCA5-AS1 (HGNC:39982): (SMARCA5 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-143514002-C-T is Benign according to our data. Variant chr4-143514002-C-T is described in ClinVar as [Benign]. Clinvar id is 740035.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=1.17 with no splicing effect.
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 AC in GnomAd at 255 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMARCA5NM_003601.4 linkuse as main transcriptc.78C>T p.Ser26= synonymous_variant 1/24 ENST00000283131.4
SMARCA5-AS1NR_104027.1 linkuse as main transcriptn.617G>A non_coding_transcript_exon_variant 2/2
SMARCA5XM_047416323.1 linkuse as main transcriptc.78C>T p.Ser26= synonymous_variant 1/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMARCA5ENST00000283131.4 linkuse as main transcriptc.78C>T p.Ser26= synonymous_variant 1/241 NM_003601.4 P1
SMARCA5-AS1ENST00000500800.2 linkuse as main transcriptn.415G>A non_coding_transcript_exon_variant 2/21

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00168
AC:
255
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000289
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00264
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00306
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00175
AC:
260
AN:
148568
Hom.:
2
AF XY:
0.00169
AC XY:
139
AN XY:
82476
show subpopulations
Gnomad AFR exome
AF:
0.000693
Gnomad AMR exome
AF:
0.000225
Gnomad ASJ exome
AF:
0.000122
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00238
Gnomad NFE exome
AF:
0.00388
Gnomad OTH exome
AF:
0.000697
GnomAD4 exome
AF:
0.00220
AC:
3070
AN:
1397500
Hom.:
5
Cov.:
31
AF XY:
0.00211
AC XY:
1457
AN XY:
691568
show subpopulations
Gnomad4 AFR exome
AF:
0.000377
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.0000793
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000123
Gnomad4 FIN exome
AF:
0.00336
Gnomad4 NFE exome
AF:
0.00263
Gnomad4 OTH exome
AF:
0.00120
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00167
AC:
255
AN:
152338
Hom.:
0
Cov.:
33
AF XY:
0.00158
AC XY:
118
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00264
Gnomad4 NFE
AF:
0.00306
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00172
Hom.:
0
Bravo
AF:
0.00138

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
-0.48
Cadd
Benign
19
Dann
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs370709174; hg19: chr4-144435155; API