rs2294752

chr1-40414280-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022733.3(SMAP2):c.571+40T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,588,576 control chromosomes in the GnomAD database, including 51,936 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 0.31 (8201 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43735 hom.)
• Consequence: SMAP2 NM_022733.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463

Genes affected

SMAP2 (HGNC:25082): (small ArfGAP2) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMAP2	NM_022733.3	c.571+40T>G		intron_variant		ENST00000372718.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMAP2	ENST00000372718.8	c.571+40T>G		intron_variant		1	NM_022733.3	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46474 AN: 152004 Hom.: 8199 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.279

GnomAD3 exomes AF: 0.252 AC: 62178 AN: 246906 Hom.: 8260 AF XY: 0.247 AC XY: 33007 AN XY: 133530

Gnomad AFR exome AF: 0.489

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.293

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.243 AC: 349146 AN: 1436454 Hom.: 43735 Cov.: 25 AF XY: 0.242 AC XY: 173276 AN XY: 716084

Gnomad4 AFR exome AF: 0.497

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.306 AC: 46496 AN: 152122 Hom.: 8201 Cov.: 32 AF XY: 0.300 AC XY: 22326 AN XY: 74390

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.275

Alfa AF: 0.261 Hom.: 1711

Bravo AF: 0.316

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	5.9
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2294752; hg19: chr1-40879952; COSMIC: COSV65531669; COSMIC: COSV65531669;