rs1014228

Variant names:

• chr3-47611149-C-T
• rs1014228
• NM_003074.4:c.2782-822G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 11 publications found

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, STRONG Submitted by: ClinGen, PanelApp Australia
• hydrocephalus, congenital, 5, susceptibility to

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

LOC124906234 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003074.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCC1	NM_003074.4	MANE Select	c.2782-822G>A		intron	N/A	NP_003065.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCC1	ENST00000254480.10	TSL:1 MANE Select	c.2782-822G>A		intron	N/A	ENSP00000254480.5	Q92922
	SMARCC1	ENST00000938791.1		c.2914-822G>A		intron	N/A	ENSP00000608850.1
	SMARCC1	ENST00000855763.1		c.2875-822G>A		intron	N/A	ENSP00000525822.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87630 AN: 151942 Hom.: 26570 Cov.: 33

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.: 33 AF XY: 0.578 AC XY: 42961 AN XY: 74330

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.38
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1014228;

hg19: chr3-47652639;