NM_016103.4:c.480+205G>C

Variant names:

• chr5-134608167-C-G
• rs329297
• NM_016103.4:c.480+205G>C

Variant summary

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

The NM_016103.4(SAR1B):​c.480+205G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 152,282 control chromosomes in the GnomAD database, including 73,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.98 (73137 hom., cov: 31)
• Consequence: SAR1B NM_016103.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.933
• Publications: 0 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=-0.97).
• BP6: Variant 5-134608167-C-G is Benign according to our data. Variant chr5-134608167-C-G is described in ClinVar as Benign. ClinVar VariationId is 1222984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016103.4. 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.480+205G>C		intron	N/A	NP_057187.1	Q9Y6B6
	SAR1B	NM_001033503.3		c.480+205G>C		intron	N/A	NP_001028675.1	Q9Y6B6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAR1B	ENST00000402673.7	TSL:1 MANE Select	c.480+205G>C		intron	N/A	ENSP00000385432.2	Q9Y6B6
	SAR1B	ENST00000439578.5	TSL:1	c.480+205G>C		intron	N/A	ENSP00000404997.1	Q9Y6B6
	SAR1B	ENST00000507419.5	TSL:1	c.276+205G>C		intron	N/A	ENSP00000425339.1	Q9H029

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149057 AN: 152164 Hom.: 73085 Cov.: 31

Gnomad AFR AF: 0.928

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.991

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.980 AC: 149168 AN: 152282 Hom.: 73137 Cov.: 31 AF XY: 0.980 AC XY: 72982 AN XY: 74460

African (AFR) AF: 0.928 AC: 38542 AN: 41532

American (AMR) AF: 0.994 AC: 15196 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 1.00 AC: 4824 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68039 AN: 68046

Other (OTH) AF: 0.991 AC: 2093 AN: 2112

Alfa AF: 0.989 Hom.: 8678

Bravo AF: 0.977

Asia WGS AF: 0.996 AC: 3461 AN: 3474

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	-0.97
CADD	Benign	7.0
DANN	Benign	0.51
PhyloP100		-0.93
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: rs329297; hg19: chr5-133943857;