rs3812692

Positions:

• chr10-70170446-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.-50C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 152,026 control chromosomes in the GnomAD database, including 69 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 0.016 (69 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SAR1A NM_020150.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAR1A	NM_020150.5	c.-50C>T		5_prime_UTR_variant	1/7	ENST00000373241.9
SAR1A	NM_001142648.2	c.-120C>T		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAR1A	ENST00000373241.9	c.-50C>T		5_prime_UTR_variant	1/7	1	NM_020150.5	P1
SAR1A	ENST00000373239.2	c.-250C>T		5_prime_UTR_variant	1/5	3
SAR1A	ENST00000373242.6	c.-120C>T		5_prime_UTR_variant	1/8	2		P1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2374 AN: 151908 Hom.: 67 Cov.: 30

Gnomad AFR AF: 0.00324

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0807

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00902

Gnomad OTH AF: 0.0192

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 154 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0156 AC: 2374 AN: 152026 Hom.: 69 Cov.: 30 AF XY: 0.0171 AC XY: 1270 AN XY: 74292

Gnomad4 AFR AF: 0.00323

Gnomad4 AMR AF: 0.0718

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0801

Gnomad4 SAS AF: 0.00561

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00902

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.0239 Hom.: 32

Bravo AF: 0.0233

Asia WGS AF: 0.0330 AC: 115 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.72
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs3812692; hg19: chr10-71930202;