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GeneBe

12-56163728-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001330288.2(SMARCC2):c.3699G>A(p.Pro1233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,506,294 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

SMARCC2
NM_001330288.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.68
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 -15 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=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-56163728-C-T is Benign according to our data. Variant chr12-56163728-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643069.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=-4.68 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000173 (235/1355184) while in subpopulation MID AF= 0.00587 (32/5450). AF 95% confidence interval is 0.00427. There are 1 homozygotes in gnomad4_exome. There are 117 alleles in male gnomad4_exome subpopulation. Median coverage is 30. 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 27 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMARCC2NM_001330288.2 linkuse as main transcriptc.3699G>A p.Pro1233= synonymous_variant 29/29 ENST00000550164.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMARCC2ENST00000550164.6 linkuse as main transcriptc.3699G>A p.Pro1233= synonymous_variant 29/295 NM_001330288.2 A2
ENST00000553176.1 linkuse as main transcriptn.213-1179G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000179
AC:
27
AN:
150992
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000122
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000659
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000960
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.000970
GnomAD3 exomes
AF:
0.000371
AC:
60
AN:
161938
Hom.:
0
AF XY:
0.000322
AC XY:
29
AN XY:
90186
show subpopulations
Gnomad AFR exome
AF:
0.000192
Gnomad AMR exome
AF:
0.000319
Gnomad ASJ exome
AF:
0.00403
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000161
Gnomad FIN exome
AF:
0.000109
Gnomad NFE exome
AF:
0.000239
Gnomad OTH exome
AF:
0.000910
GnomAD4 exome
AF:
0.000173
AC:
235
AN:
1355184
Hom.:
1
Cov.:
30
AF XY:
0.000174
AC XY:
117
AN XY:
671012
show subpopulations
Gnomad4 AFR exome
AF:
0.000265
Gnomad4 AMR exome
AF:
0.000421
Gnomad4 ASJ exome
AF:
0.00328
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000853
Gnomad4 FIN exome
AF:
0.0000777
Gnomad4 NFE exome
AF:
0.0000664
Gnomad4 OTH exome
AF:
0.000574
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000179
AC:
27
AN:
151110
Hom.:
0
Cov.:
32
AF XY:
0.000217
AC XY:
16
AN XY:
73782
show subpopulations
Gnomad4 AFR
AF:
0.000122
Gnomad4 AMR
AF:
0.0000659
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000960
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.000960
Alfa
AF:
0.000605
Hom.:
0
Bravo
AF:
0.000200

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 TuebingenAug 01, 2023SMARCC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
1.3
Dann
Benign
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

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

Other links and lift over

dbSNP: rs181267165; hg19: chr12-56557512; COSMIC: COSV53237483; COSMIC: COSV53237483; API