rs11703707

Positions:

• chr22-23802829-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003073.5(SMARCB1):​c.501-466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 299,720 control chromosomes in the GnomAD database, including 48 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 0.015 (25 hom., cov: 31)
  • Exomes 𝑓: 0.015 (23 hom.)
• Consequence: SMARCB1 NM_003073.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2229/152084) while in subpopulation NFE AF= 0.0228 (1548/67966). AF 95% confidence interval is 0.0218. There are 25 homozygotes in gnomad4. There are 1066 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2229 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCB1	NM_003073.5	c.501-466A>G		intron_variant		ENST00000644036.2	NP_003064.2
SMARCB1	NM_001362877.2	c.555-466A>G		intron_variant			NP_001349806.1
SMARCB1	NM_001317946.2	c.528-466A>G		intron_variant			NP_001304875.1
SMARCB1	NM_001007468.3	c.474-466A>G		intron_variant			NP_001007469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCB1	ENST00000644036.2	c.501-466A>G		intron_variant			NM_003073.5	ENSP00000494049.2

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2229 AN: 151966 Hom.: 25 Cov.: 31

Gnomad AFR AF: 0.00418

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0228

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.0155 AC: 2282 AN: 147636 Hom.: 23 Cov.: 0 AF XY: 0.0146 AC XY: 1157 AN XY: 79390

Gnomad4 AFR exome AF: 0.00306

Gnomad4 AMR exome AF: 0.00832

Gnomad4 ASJ exome AF: 0.00800

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00743

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0207

Gnomad4 OTH exome AF: 0.0139

GnomAD4 genome AF: 0.0147 AC: 2229 AN: 152084 Hom.: 25 Cov.: 31 AF XY: 0.0143 AC XY: 1066 AN XY: 74348

Gnomad4 AFR AF: 0.00417

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00561

Gnomad4 FIN AF: 0.0206

Gnomad4 NFE AF: 0.0228

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0205 Hom.: 5

Bravo AF: 0.0135

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.45
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

Publications

LitVar

Other links and lift over

dbSNP: rs11703707; hg19: chr22-24145016;