rs2271690

chr10-70161835-G-A

Variant summary

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

The NM_020150.5(SAR1A):c.58+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,611,708 control chromosomes in the GnomAD database, including 87,549 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 0.27 (6478 hom., cov: 32)
  • Exomes 𝑓: 0.33 (81071 hom.)
• Consequence: SAR1A NM_020150.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

Genes affected

SAR1A (HGNC:10534): (secretion associated Ras related GTPase 1A) Predicted to enable GTPase activity. Involved in COPII-coated vesicle cargo loading. Part of COPII vesicle coat. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAR1A	NM_020150.5	c.58+23C>T		intron_variant		ENST00000373241.9
SAR1A	NM_001142648.2	c.58+23C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAR1A	ENST00000373241.9	c.58+23C>T		intron_variant		1	NM_020150.5	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40411 AN: 151972 Hom.: 6470 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.320 AC: 80409 AN: 251226 Hom.: 14220 AF XY: 0.314 AC XY: 42649 AN XY: 135792

Gnomad AFR exome AF: 0.0746

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.436

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.324

Gnomad OTH exome AF: 0.329

GnomAD4 exome AF: 0.327 AC: 476599 AN: 1459618 Hom.: 81071 Cov.: 32 AF XY: 0.324 AC XY: 235179 AN XY: 726232

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.266 AC: 40422 AN: 152090 Hom.: 6478 Cov.: 32 AF XY: 0.265 AC XY: 19690 AN XY: 74354

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.298

Alfa AF: 0.325 Hom.: 12312

Bravo AF: 0.277

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.96
Dann	Benign	0.35
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: rs2271690; hg19: chr10-71921591; COSMIC: COSV64698184; COSMIC: COSV64698184;