rs2267032

Variant names:

• chr22-23806086-A-G
• rs2267032
• NM_003073.5:c.628+2664A>G

Variant summary

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

The ENST00000644036.2(SMARCB1):​c.628+2664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,106 control chromosomes in the GnomAD database, including 38,086 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 0.69 (38086 hom., cov: 33)
• Consequence: SMARCB1 ENST00000644036.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 16 publications found

Genes affected

SMARCB1 (HGNC:11103): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) The protein encoded by this gene is part of a complex that relieves repressive chromatin structures, allowing the transcriptional machinery to access its targets more effectively. The encoded nuclear protein may also bind to and enhance the DNA joining activity of HIV-1 integrase. This gene has been found to be a tumor suppressor, and mutations in it have been associated with malignant rhabdoid tumors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

SMARCB1 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• intellectual disability, autosomal dominant 15

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• rhabdoid tumor predisposition syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• SMARCB1-related schwannomatosis

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
• familial multiple meningioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial rhabdoid tumor

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schwannomatosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000644036.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCB1	NM_003073.5	MANE Select	c.628+2664A>G		intron	N/A	NP_003064.2
	SMARCB1	NM_001362877.2		c.682+2664A>G		intron	N/A	NP_001349806.1
	SMARCB1	NM_001317946.2		c.655+2664A>G		intron	N/A	NP_001304875.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCB1	ENST00000644036.2	MANE Select	c.628+2664A>G		intron	N/A	ENSP00000494049.2
	SMARCB1	ENST00000407422.8	TSL:1	c.601+2664A>G		intron	N/A	ENSP00000383984.3
	SMARCB1	ENST00000263121.12	TSL:1	c.490+2664A>G		intron	N/A	ENSP00000263121.8

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105621 AN: 151988 Hom.: 38088 Cov.: 33

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.695 AC: 105642 AN: 152106 Hom.: 38086 Cov.: 33 AF XY: 0.694 AC XY: 51558 AN XY: 74328

African (AFR) AF: 0.491 AC: 20382 AN: 41478

American (AMR) AF: 0.756 AC: 11542 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2691 AN: 3472

East Asian (EAS) AF: 0.624 AC: 3223 AN: 5162

South Asian (SAS) AF: 0.539 AC: 2600 AN: 4820

European-Finnish (FIN) AF: 0.808 AC: 8551 AN: 10586

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.799 AC: 54349 AN: 67994

Other (OTH) AF: 0.694 AC: 1468 AN: 2114

Alfa AF: 0.729 Hom.: 45434

Bravo AF: 0.685

Asia WGS AF: 0.585 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.094
DANN	Benign	0.36
PhyloP100		-1.2
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: rs2267032; hg19: chr22-24148273;