22-23801315-C-T

Variant names:

• chr22-23801315-C-T
• rs738797
• ENST00000491967.2:n.897C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000491967.2(SMARCB1):​n.897C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 567,526 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: SMARCB1 ENST00000491967.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491967.2. 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.500+234C>T		intron	N/A	NP_003064.2
	SMARCB1	NM_001362877.2		c.554+180C>T		intron	N/A	NP_001349806.1
	SMARCB1	NM_001317946.2		c.527+180C>T		intron	N/A	NP_001304875.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCB1	ENST00000491967.2	TSL:1	n.897C>T		non_coding_transcript_exon	Exon 4 of 4
	SMARCB1	ENST00000644036.2	MANE Select	c.500+234C>T		intron	N/A	ENSP00000494049.2
	SMARCB1	ENST00000407422.8	TSL:1	c.473+234C>T		intron	N/A	ENSP00000383984.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000761 AC: 1 AN: 131416 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000176 AC: 1 AN: 567526 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 306244

African (AFR) AF: 0.00 AC: 0 AN: 16058

American (AMR) AF: 0.0000288 AC: 1 AN: 34668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20086

East Asian (EAS) AF: 0.00 AC: 0 AN: 32094

South Asian (SAS) AF: 0.00 AC: 0 AN: 62288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 333976

Other (OTH) AF: 0.00 AC: 0 AN: 31126

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 6445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.54
PhyloP100		-0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs738797; hg19: chr22-24143502;