rs6857360

Variant names:

• chr4-143524636-C-T
• rs6857360
• NM_003601.4:c.520+169C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003601.4(SMARCA5):​c.520+169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,926 control chromosomes in the GnomAD database, including 16,648 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16648 hom., cov: 32)
• Consequence: SMARCA5 NM_003601.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003601.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA5	NM_003601.4	MANE Select	c.520+169C>T		intron	N/A	NP_003592.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA5	ENST00000283131.4	TSL:1 MANE Select	c.520+169C>T		intron	N/A	ENSP00000283131.3	O60264
	SMARCA5	ENST00000940952.1		c.562+169C>T		intron	N/A	ENSP00000611011.1
	SMARCA5	ENST00000940953.1		c.544+169C>T		intron	N/A	ENSP00000611012.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70326 AN: 151808 Hom.: 16620 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70395 AN: 151926 Hom.: 16648 Cov.: 32 AF XY: 0.462 AC XY: 34295 AN XY: 74232

African (AFR) AF: 0.509 AC: 21057 AN: 41400

American (AMR) AF: 0.448 AC: 6854 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3470

East Asian (EAS) AF: 0.739 AC: 3819 AN: 5170

South Asian (SAS) AF: 0.469 AC: 2258 AN: 4818

European-Finnish (FIN) AF: 0.395 AC: 4168 AN: 10548

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29173 AN: 67918

Other (OTH) AF: 0.464 AC: 978 AN: 2106

Alfa AF: 0.456 Hom.: 2603

Bravo AF: 0.470

Asia WGS AF: 0.551 AC: 1914 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.35
PhyloP100		-0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6857360; hg19: chr4-144445789;