dbSNP rs1014228: SMARCC1:c.2782-822G>A (chr3-47611149-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003074.4(SMARCC1):c.2782-822G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,060 control chromosomes in the GnomAD database, including 26,570 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 26570 hom., cov: 33)

Consequence

SMARCC1
NM_003074.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.342

Publications

11 publications found

Variant links:

Genes affected

SMARCC1 (HGNC:11104): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 1) 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. [provided by RefSeq, Jul 2008]

SMARCC1 Gene-Disease associations (from GenCC):

SMARCC1-associated developmental dysgenesis syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hydrocephalus, congenital, 5, susceptibility to
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

SMARCC1 links:

LOC124906234 (HGNC:):

LOC124906234 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCC1	NM_003074.4 link	c.2782-822G>A		intron_variant	Intron 25 of 27	ENST00000254480.10	NP_003065.3	Q92922Q58EY4
LOC124906234	XR_007095902.1 link	n.127-3151C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCC1	ENST00000254480.10 link	c.2782-822G>A		intron_variant	Intron 25 of 27	1	NM_003074.4	ENSP00000254480.5		Q92922
SMARCC1	ENST00000425518.5 link	n.2672-822G>A		intron_variant	Intron 25 of 27	2

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87630

AN:

151942

Hom.:

26570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.574

Gnomad EAS

AF:

0.598

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.576

AC:

87654

AN:

152060

Hom.:

26570

Cov.:

AF XY:

0.578

AC XY:

42961

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.399

AC:

16540

AN:

41444

American (AMR)

AF:

0.492

AC:

7508

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.574

AC:

1993

AN:

3470

East Asian (EAS)

AF:

0.598

AC:

3097

AN:

5180

South Asian (SAS)

AF:

0.533

AC:

2567

AN:

4818

European-Finnish (FIN)

AF:

0.750

AC:

7931

AN:

10580

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.676

AC:

45975

AN:

67982

Other (OTH)

AF:

0.571

AC:

1209

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1788

3576

5365

7153

8941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.623

Hom.:

37915

Bravo

AF:

0.547

Asia WGS

AF:

0.544

AC:

1894

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.66

(source)

DANN

Benign

0.38

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over