Variant 4-143514002-C-T details in Genebe, Genetics Data Aggregator

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.Ser26Ser) 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

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 links:

SMARCA5-AS1 (HGNC:):

SMARCA5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

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

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BS2

High AC in GnomAd4 at 255 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA5	NM_003601.4 linkuse as main transcript	c.78C>T	p.Ser26Ser	synonymous_variant	1/24	ENST00000283131.4	NP_003592.3	O60264
SMARCA5	XM_047416323.1 linkuse as main transcript	c.78C>T	p.Ser26Ser	synonymous_variant	1/14		XP_047272279.1
SMARCA5-AS1	NR_104027.1 linkuse as main transcript	n.617G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA5	ENST00000283131.4 linkuse as main transcript	c.78C>T	p.Ser26Ser	synonymous_variant	1/24	1	NM_003601.4	ENSP00000283131.3		O60264
SMARCA5-AS1	ENST00000500800.2 linkuse as main transcript	n.415G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

152220

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00167

AC:

255

AN:

152338

Hom.:

Cov.:

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.:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

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.

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