NM_003074.4:c.1900-3730G>T

Variant names:

• chr3-47666322-C-A
• rs11130146
• NM_003074.4:c.1900-3730G>T

Variant summary

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

The NM_003074.4(SMARCC1):​c.1900-3730G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,026 control chromosomes in the GnomAD database, including 28,194 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 0.60 (28194 hom., cov: 31)
• Consequence: SMARCC1 NM_003074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (EAS) allele frequency at 95% confidence interval = 0.702 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.1900-3730G>T		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.1900-3730G>T		intron	N/A	ENSP00000254480.5	Q92922
	SMARCC1	ENST00000938791.1		c.1900-3730G>T		intron	N/A	ENSP00000608850.1
	SMARCC1	ENST00000855763.1		c.1993-3730G>T		intron	N/A	ENSP00000525822.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90461 AN: 151908 Hom.: 28193 Cov.: 31

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.595 AC: 90497 AN: 152026 Hom.: 28194 Cov.: 31 AF XY: 0.600 AC XY: 44586 AN XY: 74292

African (AFR) AF: 0.403 AC: 16708 AN: 41448

American (AMR) AF: 0.608 AC: 9281 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3472

East Asian (EAS) AF: 0.721 AC: 3717 AN: 5156

South Asian (SAS) AF: 0.540 AC: 2601 AN: 4820

European-Finnish (FIN) AF: 0.769 AC: 8133 AN: 10572

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 45987 AN: 67970

Other (OTH) AF: 0.587 AC: 1238 AN: 2108

Alfa AF: 0.637 Hom.: 16014

Bravo AF: 0.576

Asia WGS AF: 0.582 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-0.086
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

Other links and lift over

dbSNP: rs11130146; hg19: chr3-47707812;