10-70170487-G-T

Variant names:

• chr10-70170487-G-T
• rs3812693
• NM_020150.5:c.-91C>A

Variant summary

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

The NM_020150.5(SAR1A):​c.-91C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 152,726 control chromosomes in the GnomAD database, including 108 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 0.026 (107 hom., cov: 30)
  • Exomes 𝑓: 0.032 (1 hom.)
• Consequence: SAR1A NM_020150.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAR1A	NM_020150.5	c.-91C>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000373241.9	NP_064535.1
SAR1A	NM_001142648.2	c.-161C>A		5_prime_UTR_variant	Exon 1 of 8		NP_001136120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAR1A	ENST00000373241.9	c.-91C>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_020150.5	ENSP00000362338.4
SAR1A	ENST00000373242.6	c.-161C>A		5_prime_UTR_variant	Exon 1 of 8	2		ENSP00000362339.1
SAR1A	ENST00000373239.2	c.-291C>A		5_prime_UTR_variant	Exon 1 of 5	3		ENSP00000362336.2

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3959 AN: 151960 Hom.: 107 Cov.: 30

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0376

Gnomad FIN AF: 0.00972

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0324 AC: 21 AN: 648 Hom.: 1 Cov.: 0 AF XY: 0.0300 AC XY: 15 AN XY: 500

African (AFR) AF: 0.00 AC: 0 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.179 AC: 5 AN: 28

South Asian (SAS) AF: 0.0625 AC: 2 AN: 32

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0264 AC: 14 AN: 530

Other (OTH) AF: 0.00 AC: 0 AN: 28

GnomAD4 genome AF: 0.0260 AC: 3956 AN: 152078 Hom.: 107 Cov.: 30 AF XY: 0.0270 AC XY: 2003 AN XY: 74322

African (AFR) AF: 0.0306 AC: 1271 AN: 41514

American (AMR) AF: 0.0222 AC: 339 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.146 AC: 751 AN: 5136

South Asian (SAS) AF: 0.0376 AC: 181 AN: 4814

European-Finnish (FIN) AF: 0.00972 AC: 103 AN: 10602

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0175 AC: 1186 AN: 67954

Other (OTH) AF: 0.0246 AC: 52 AN: 2110

Alfa AF: 0.0168 Hom.: 20

Bravo AF: 0.0272

Asia WGS AF: 0.0870 AC: 302 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.089
DANN	Benign	0.93
PhyloP100		-3.3
PromoterAI		-0.089	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3812693; hg19: chr10-71930243;