22-23791306-C-T

Variant names:

• chr22-23791306-C-T
• rs2073389
• NM_003073.5:c.94-450C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003073.5(SMARCB1):​c.94-450C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,066 control chromosomes in the GnomAD database, including 29,581 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 0.59 (29581 hom., cov: 34)
• Consequence: SMARCB1 NM_003073.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423
• 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: ClinGen, Orphanet
• intellectual disability, autosomal dominant 15

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

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp, G2P
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003073.5. 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
	SMARCB1	NM_003073.5	MANE Select	c.94-450C>T		intron	N/A	NP_003064.2
	SMARCB1	NM_001362877.2		c.94-450C>T		intron	N/A	NP_001349806.1
	SMARCB1	NM_001317946.2		c.94-450C>T		intron	N/A	NP_001304875.1	G5E975

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCB1	ENST00000644036.2	MANE Select	c.94-450C>T		intron	N/A	ENSP00000494049.2	Q12824-1
	SMARCB1	ENST00000407422.8	TSL:1	c.94-450C>T		intron	N/A	ENSP00000383984.3	Q12824-2
	SMARCB1	ENST00000263121.12	TSL:1	c.94-450C>T		intron	N/A	ENSP00000263121.8	A0A0G2JRV3

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89963 AN: 151946 Hom.: 29589 Cov.: 34

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.592 AC: 89958 AN: 152066 Hom.: 29581 Cov.: 34 AF XY: 0.595 AC XY: 44204 AN XY: 74332

African (AFR) AF: 0.279 AC: 11552 AN: 41426

American (AMR) AF: 0.703 AC: 10736 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2372 AN: 3472

East Asian (EAS) AF: 0.564 AC: 2919 AN: 5178

South Asian (SAS) AF: 0.630 AC: 3040 AN: 4826

European-Finnish (FIN) AF: 0.756 AC: 7991 AN: 10568

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49271 AN: 68000

Other (OTH) AF: 0.605 AC: 1278 AN: 2112

Alfa AF: 0.634 Hom.: 4255

Bravo AF: 0.573

Asia WGS AF: 0.577 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		0.42
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: rs2073389; hg19: chr22-24133493;