chr12-56171027-G-A

Variant names:

• chr12-56171027-G-A
• rs7960225
• NM_001330288.2:c.2347+244C>T

Variant summary

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

The NM_001330288.2(SMARCC2):​c.2347+244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,886 control chromosomes in the GnomAD database, including 7,710 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 0.29 (7710 hom., cov: 31)
• Consequence: SMARCC2 NM_001330288.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Coffin-Siris syndrome 8

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000258199 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCC2	NM_001330288.2	c.2347+244C>T		intron_variant	Intron 22 of 28	ENST00000550164.6	NP_001317217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCC2	ENST00000550164.6	c.2347+244C>T		intron_variant	Intron 22 of 28	5	NM_001330288.2	ENSP00000449396.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43997 AN: 151768 Hom.: 7709 Cov.: 31

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.290 AC: 43986 AN: 151886 Hom.: 7710 Cov.: 31 AF XY: 0.295 AC XY: 21858 AN XY: 74208

African (AFR) AF: 0.0857 AC: 3552 AN: 41426

American (AMR) AF: 0.401 AC: 6132 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1126 AN: 3466

East Asian (EAS) AF: 0.437 AC: 2254 AN: 5154

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4814

European-Finnish (FIN) AF: 0.383 AC: 4034 AN: 10520

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24533 AN: 67926

Other (OTH) AF: 0.336 AC: 704 AN: 2098

Alfa AF: 0.349 Hom.: 13385

Bravo AF: 0.287

Asia WGS AF: 0.303 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.025
DANN	Benign	0.62
PhyloP100		-2.6
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: rs7960225; hg19: chr12-56564811;