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GeneBe

12-56164613-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001330288.2(SMARCC2):c.3351G>A(p.Pro1117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,613,342 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 5 hom. )

Consequence

SMARCC2
NM_001330288.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.623
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-56164613-C-T is Benign according to our data. Variant chr12-56164613-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1711343.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.623 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00153 (232/152106) while in subpopulation NFE AF= 0.00266 (181/67988). AF 95% confidence interval is 0.00234. There are 0 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 232 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMARCC2NM_001330288.2 linkuse as main transcriptc.3351G>A p.Pro1117= synonymous_variant 28/29 ENST00000550164.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMARCC2ENST00000550164.6 linkuse as main transcriptc.3351G>A p.Pro1117= synonymous_variant 28/295 NM_001330288.2 A2
ENST00000553176.1 linkuse as main transcriptn.213-2064G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00153
AC:
232
AN:
151988
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000508
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.000567
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00266
Gnomad OTH
AF:
0.00240
GnomAD3 exomes
AF:
0.00107
AC:
267
AN:
249664
Hom.:
0
AF XY:
0.00115
AC XY:
155
AN XY:
135028
show subpopulations
Gnomad AFR exome
AF:
0.000310
Gnomad AMR exome
AF:
0.000874
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.000280
Gnomad NFE exome
AF:
0.00194
Gnomad OTH exome
AF:
0.000984
GnomAD4 exome
AF:
0.00176
AC:
2572
AN:
1461236
Hom.:
5
Cov.:
32
AF XY:
0.00177
AC XY:
1288
AN XY:
726894
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.000964
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000928
Gnomad4 FIN exome
AF:
0.000394
Gnomad4 NFE exome
AF:
0.00217
Gnomad4 OTH exome
AF:
0.00119
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00153
AC:
232
AN:
152106
Hom.:
0
Cov.:
32
AF XY:
0.00148
AC XY:
110
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.000506
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.000567
Gnomad4 NFE
AF:
0.00266
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00110
Hom.:
0
Bravo
AF:
0.00139

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023SMARCC2: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
11
Dann
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs75924441; hg19: chr12-56558397; API