5-134606802-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016103.4(SAR1B):c.*148A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 682,524 control chromosomes in the GnomAD database, including 9,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2055 hom., cov: 32)
  • Exomes 𝑓: 0.15 (7758 hom.)
• Consequence: SAR1B NM_016103.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.623

Genes affected

SAR1B (HGNC:10535): (secretion associated Ras related GTPase 1B) The protein encoded by this gene is a small GTPase that acts as a homodimer. The encoded protein is activated by the guanine nucleotide exchange factor PREB and is involved in protein transport from the endoplasmic reticulum to the Golgi. This protein is part of the COPII coat complex. Defects in this gene are a cause of chylomicron retention disease (CMRD), also known as Anderson disease (ANDD). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 5-134606802-T-C is Benign according to our data. Variant chr5-134606802-T-C is described in ClinVar as [Benign]. Clinvar id is 1247459.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-134606802-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAR1B	NM_016103.4	c.*148A>G		3_prime_UTR_variant	7/7	ENST00000402673.7
SAR1B	NM_001033503.3	c.*148A>G		3_prime_UTR_variant	8/8
SAR1B	XM_047417257.1	c.*148A>G		3_prime_UTR_variant	7/7
SAR1B	XM_047417258.1	c.*148A>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAR1B	ENST00000402673.7	c.*148A>G		3_prime_UTR_variant	7/7	1	NM_016103.4	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23863 AN: 152090 Hom.: 2046 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.155 AC: 81996 AN: 530316 Hom.: 7758 Cov.: 5 AF XY: 0.153 AC XY: 44073 AN XY: 288532

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.157 AC: 23895 AN: 152208 Hom.: 2055 Cov.: 32 AF XY: 0.161 AC XY: 11953 AN XY: 74424

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.154

Alfa AF: 0.126 Hom.: 2424

Bravo AF: 0.164

Asia WGS AF: 0.253 AC: 877 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	14
Dann	Benign	0.85

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: rs7728741; hg19: chr5-133942492; COSMIC: COSV68391524; COSMIC: COSV68391524;