4-143524636-C-T

Position:

• chr4-143524636-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA5	NM_003601.4	c.520+169C>T		intron_variant		ENST00000283131.4	NP_003592.3
SMARCA5	XM_047416323.1	c.520+169C>T		intron_variant			XP_047272279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA5	ENST00000283131.4	c.520+169C>T		intron_variant		1	NM_003601.4	ENSP00000283131.3

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

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.464

Alfa AF: 0.454 Hom.: 2497

Bravo AF: 0.470

Asia WGS AF: 0.551 AC: 1914 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.35
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

Other links and lift over

dbSNP: rs6857360; hg19: chr4-144445789;