17-40628675-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003079.5(SMARCE1):c.*110C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 783,098 control chromosomes in the GnomAD database, including 13,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3944 hom., cov: 33)
  • Exomes 𝑓: 0.15 (9409 hom.)
• Consequence: SMARCE1 NM_003079.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.199

Genes affected

SMARCE1 (HGNC:11109): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1) The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 17-40628675-G-A is Benign according to our data. Variant chr17-40628675-G-A is described in ClinVar as [Benign]. Clinvar id is 1230941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCE1	NM_003079.5	c.*110C>T		3_prime_UTR_variant	11/11	ENST00000348513.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCE1	ENST00000348513.12	c.*110C>T		3_prime_UTR_variant	11/11	1	NM_003079.5	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30693 AN: 152030 Hom.: 3918 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.147 AC: 92568 AN: 630950 Hom.: 9409 Cov.: 8 AF XY: 0.143 AC XY: 47604 AN XY: 332202

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.0689

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.202 AC: 30778 AN: 152148 Hom.: 3944 Cov.: 33 AF XY: 0.207 AC XY: 15363 AN XY: 74386

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.172

Alfa AF: 0.129 Hom.: 2250

Bravo AF: 0.222

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	10
Dann	Benign	0.73
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0

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: rs757412; hg19: chr17-38784927; COSMIC: COSV52860744; COSMIC: COSV52860744;