rs199737164

chr22-23801105-C-Achr22-23801105-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003073.5(SMARCB1):c.500+24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: SMARCB1 NM_003073.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11521673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCB1	NM_003073.5	c.500+24C>A		intron_variant		ENST00000644036.2
SMARCB1	NM_001362877.2	c.524C>A	p.Thr175Asn	missense_variant	4/9
SMARCB1	NM_001317946.2	c.497C>A	p.Thr166Asn	missense_variant	4/9
SMARCB1	NM_001007468.3	c.473+24C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCB1	ENST00000644036.2	c.500+24C>A		intron_variant			NM_003073.5	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	2.0
Dann	Benign	0.96
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.061	N
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.36	T
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.12
Sift	Benign	0.14	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0	B;.
Vest4		0.16
MutPred		0.51		Gain of MoRF binding (P = 0.2716);.;
MVP		0.32
ClinPred		0.70	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-24143292;