chr5-134606802-T-C

Variant names:

• chr5-134606802-T-C
• rs7728741
• ENST00000439578.5:c.*148A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000439578.5(SAR1B):​c.*148A>G variant causes a splice region 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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 ENST00000439578.5 splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.623
• Publications: 14 publications found

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]

SAR1B Gene-Disease associations (from GenCC):

• chylomicron retention disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1247459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000439578.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAR1B	NM_016103.4	MANE Select	c.*148A>G		3_prime_UTR	Exon 7 of 7	NP_057187.1	Q9Y6B6
	SAR1B	NM_001033503.3		c.*148A>G		3_prime_UTR	Exon 8 of 8	NP_001028675.1	Q9Y6B6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAR1B	ENST00000439578.5	TSL:1	c.*148A>G		splice_region	Exon 8 of 8	ENSP00000404997.1	Q9Y6B6
	SAR1B	ENST00000402673.7	TSL:1 MANE Select	c.*148A>G		3_prime_UTR	Exon 7 of 7	ENSP00000385432.2	Q9Y6B6
	SAR1B	ENST00000439578.5	TSL:1	c.*148A>G		3_prime_UTR	Exon 8 of 8	ENSP00000404997.1	Q9Y6B6

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

African (AFR) AF: 0.179 AC: 2507 AN: 13994

American (AMR) AF: 0.285 AC: 9221 AN: 32300

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 1944 AN: 18232

East Asian (EAS) AF: 0.355 AC: 10738 AN: 30246

South Asian (SAS) AF: 0.174 AC: 10628 AN: 61018

European-Finnish (FIN) AF: 0.190 AC: 7401 AN: 39040

Middle Eastern (MID) AF: 0.150 AC: 561 AN: 3734

European-Non Finnish (NFE) AF: 0.115 AC: 34950 AN: 303318

Other (OTH) AF: 0.142 AC: 4046 AN: 28434

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

African (AFR) AF: 0.178 AC: 7393 AN: 41526

American (AMR) AF: 0.228 AC: 3485 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1639 AN: 5172

South Asian (SAS) AF: 0.179 AC: 862 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1941 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7798 AN: 68000

Other (OTH) AF: 0.154 AC: 326 AN: 2114

Alfa AF: 0.133 Hom.: 4281

Bravo AF: 0.164

Asia WGS AF: 0.253 AC: 877 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.62
Mutation Taster		=100/0	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: rs7728741; hg19: chr5-133942492; COSMIC: COSV68391524; COSMIC: COSV68391524;