Genetic Variant SMARCC2:p.Pro1233Pro (chr12-56163728-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001330288.2(SMARCC2):c.3699G>A(p.Pro1233Pro) 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

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.68

Publications

3 publications found

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]

SMARCC2 links:

ENSG00000258199 (HGNC:):

ENSG00000258199 links:

MYL6 (HGNC:7587): (myosin light chain 6) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain that is expressed in smooth muscle and non-muscle tissues. Genomic sequences representing several pseudogenes have been described and two transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MYL6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 12-56163728-C-T is Benign according to our data. Variant chr12-56163728-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643069.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.68 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 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 GnomAdExome4. There are 117 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 27 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330288.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCC2	NM_001330288.2	MANE Select	c.3699G>A	p.Pro1233Pro	synonymous	Exon 29 of 29	NP_001317217.1	F8VXC8
SMARCC2	NM_003075.5		c.3606G>A	p.Pro1202Pro	synonymous	Exon 28 of 28	NP_003066.2
SMARCC2	NM_001130420.3		c.3420G>A	p.Pro1140Pro	synonymous	Exon 30 of 30	NP_001123892.1	Q8TAQ2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMARCC2	ENST00000550164.6	TSL:5 MANE Select	c.3699G>A	p.Pro1233Pro	synonymous	Exon 29 of 29	ENSP00000449396.1	F8VXC8
SMARCC2	ENST00000267064.8	TSL:1	c.3606G>A	p.Pro1202Pro	synonymous	Exon 28 of 28	ENSP00000267064.4	Q8TAQ2-1
SMARCC2	ENST00000394023.7	TSL:1	c.3420G>A	p.Pro1140Pro	synonymous	Exon 30 of 30	ENSP00000377591.3	Q8TAQ2-3

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

150992

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000371

AC:

AN:

161938

AF XY:

0.000322

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 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.:

Cov.:

AF XY:

0.000174

AC XY:

117

AN XY:

671012

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

26450

American (AMR)

AF:

0.000421

AC:

AN:

21390

Ashkenazi Jewish (ASJ)

AF:

0.00328

AC:

AN:

22586

East Asian (EAS)

AF:

0.00

AC:

AN:

32066

South Asian (SAS)

AF:

0.0000853

AC:

AN:

70354

European-Finnish (FIN)

AF:

0.0000777

AC:

AN:

51486

Middle Eastern (MID)

AF:

0.00587

AC:

AN:

5450

European-Non Finnish (NFE)

AF:

0.0000664

AC:

AN:

1069632

Other (OTH)

AF:

0.000574

AC:

AN:

55770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000179

AC:

AN:

151110

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

AN XY:

73782

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

41082

American (AMR)

AF:

0.0000659

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4736

European-Finnish (FIN)

AF:

0.0000960

AC:

AN:

10422

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

67808

Other (OTH)

AF:

0.000960

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000605

Hom.:

Bravo

AF:

0.000200

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.3

(source)

DANN

Benign

0.74

PhyloP100

-4.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over