1-40406951-C-T

Variant names:

• chr1-40406951-C-T
• rs2982510
• NM_022733.3:c.237+82C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022733.3(SMAP2):​c.237+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,454,244 control chromosomes in the GnomAD database, including 47,405 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 0.30 (8105 hom., cov: 32)
  • Exomes 𝑓: 0.24 (39300 hom.)
• Consequence: SMAP2 NM_022733.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMAP2	NM_022733.3	c.237+82C>T		intron_variant	Intron 2 of 9	ENST00000372718.8	NP_073570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMAP2	ENST00000372718.8	c.237+82C>T		intron_variant	Intron 2 of 9	1	NM_022733.3	ENSP00000361803.3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46271 AN: 151996 Hom.: 8105 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.241 AC: 314133 AN: 1302130 Hom.: 39300 AF XY: 0.240 AC XY: 153991 AN XY: 641500

African (AFR) AF: 0.494 AC: 14318 AN: 28978

American (AMR) AF: 0.241 AC: 7530 AN: 31256

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 4457 AN: 20718

East Asian (EAS) AF: 0.273 AC: 9948 AN: 36416

South Asian (SAS) AF: 0.228 AC: 15258 AN: 67060

European-Finnish (FIN) AF: 0.198 AC: 9572 AN: 48242

Middle Eastern (MID) AF: 0.213 AC: 916 AN: 4296

European-Non Finnish (NFE) AF: 0.236 AC: 238922 AN: 1012030

Other (OTH) AF: 0.249 AC: 13212 AN: 53134

GnomAD4 genome AF: 0.304 AC: 46287 AN: 152114 Hom.: 8105 Cov.: 32 AF XY: 0.299 AC XY: 22223 AN XY: 74356

African (AFR) AF: 0.484 AC: 20088 AN: 41480

American (AMR) AF: 0.261 AC: 3997 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1515 AN: 5188

South Asian (SAS) AF: 0.228 AC: 1098 AN: 4822

European-Finnish (FIN) AF: 0.187 AC: 1981 AN: 10576

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16170 AN: 67970

Other (OTH) AF: 0.274 AC: 580 AN: 2114

Alfa AF: 0.258 Hom.: 23016

Bravo AF: 0.315

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.50
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2982510; hg19: chr1-40872623; COSMIC: COSV65532418;