rs757412

Variant names:

• chr17-40628675-G-A
• rs757412
• NM_003079.5:c.*110C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.199
• Publications: 16 publications found

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]

SMARCE1 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• familial meningioma

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, ClinGen, Ambry Genetics
• Coffin-Siris syndrome 5

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• familial multiple meningioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000264058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1230941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003079.5. 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
	SMARCE1	NM_003079.5	MANE Select	c.*110C>T		3_prime_UTR	Exon 11 of 11	NP_003070.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCE1	ENST00000348513.12	TSL:1 MANE Select	c.*110C>T		3_prime_UTR	Exon 11 of 11	ENSP00000323967.6	Q969G3-1
	SMARCE1	ENST00000377808.9	TSL:1	c.*333C>T		3_prime_UTR	Exon 11 of 11	ENSP00000367039.4	Q969G3-5
	SMARCE1	ENST00000580419.6	TSL:1	c.*325C>T		3_prime_UTR	Exon 10 of 10	ENSP00000462475.2	A0A2U3TZQ7

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

African (AFR) AF: 0.310 AC: 5095 AN: 16430

American (AMR) AF: 0.426 AC: 12792 AN: 30050

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 1138 AN: 16528

East Asian (EAS) AF: 0.292 AC: 9941 AN: 34004

South Asian (SAS) AF: 0.142 AC: 7834 AN: 55104

European-Finnish (FIN) AF: 0.158 AC: 5529 AN: 34974

Middle Eastern (MID) AF: 0.0710 AC: 281 AN: 3960

European-Non Finnish (NFE) AF: 0.111 AC: 45146 AN: 407510

Other (OTH) AF: 0.149 AC: 4812 AN: 32390

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

African (AFR) AF: 0.316 AC: 13104 AN: 41482

American (AMR) AF: 0.316 AC: 4831 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3468

East Asian (EAS) AF: 0.350 AC: 1814 AN: 5188

South Asian (SAS) AF: 0.154 AC: 742 AN: 4822

European-Finnish (FIN) AF: 0.174 AC: 1838 AN: 10586

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7756 AN: 67992

Other (OTH) AF: 0.172 AC: 363 AN: 2114

Alfa AF: 0.140 Hom.: 3426

Bravo AF: 0.222

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		0.20
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
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: rs757412; hg19: chr17-38784927; COSMIC: COSV52860744; COSMIC: COSV52860744;