12-56163804-G-A

Variant summary

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

The NM_001330288.2(SMARCC2):c.3662-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,371,192 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (80 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (39 hom.)
• Consequence: SMARCC2 NM_001330288.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.03

Genes affected

SMARCC2 (HGNC:11105): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-56163804-G-A is Benign according to our data. Variant chr12-56163804-G-A is described in ClinVar as [Benign]. Clinvar id is 1283609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCC2	NM_001330288.2	c.3662-39C>T		intron_variant		ENST00000550164.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCC2	ENST00000550164.6	c.3662-39C>T		intron_variant		5	NM_001330288.2	A2
	ENST00000553176.1	n.213-1255C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2716 AN: 152046 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00649

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00401 AC: 448 AN: 111760 Hom.: 14 AF XY: 0.00268 AC XY: 167 AN XY: 62350

Gnomad AFR exome AF: 0.0659

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000277

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00319

GnomAD4 exome AF: 0.00146 AC: 1774 AN: 1219028 Hom.: 39 Cov.: 17 AF XY: 0.00135 AC XY: 820 AN XY: 606140

Gnomad4 AFR exome AF: 0.0596

Gnomad4 AMR exome AF: 0.00362

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000328

Gnomad4 SAS exome AF: 0.000187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000607

Gnomad4 OTH exome AF: 0.00372

GnomAD4 genome AF: 0.0179 AC: 2720 AN: 152164 Hom.: 80 Cov.: 32 AF XY: 0.0172 AC XY: 1278 AN XY: 74386

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.00648

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00917 Hom.: 5

Bravo AF: 0.0196

Asia WGS AF: 0.00346 AC: 12 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

May 23, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.7
Dann	Benign	0.52
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: rs74092007; hg19: chr12-56557588;