5-134608167-C-G

Variant names:

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

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=-0.97).
• BP6: Variant 5-134608167-C-G is Benign according to our data. Variant chr5-134608167-C-G is described in ClinVar as [Benign]. Clinvar id is 1222984.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-134608167-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAR1B	NM_016103.4	c.480+205G>C		intron_variant	Intron 6 of 6	ENST00000402673.7	NP_057187.1
SAR1B	NM_001033503.3	c.480+205G>C		intron_variant	Intron 7 of 7		NP_001028675.1
SAR1B	XM_047417257.1	c.480+205G>C		intron_variant	Intron 6 of 6		XP_047273213.1
SAR1B	XM_047417258.1	c.276+205G>C		intron_variant	Intron 4 of 4		XP_047273214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAR1B	ENST00000402673.7	c.480+205G>C		intron_variant	Intron 6 of 6	1	NM_016103.4	ENSP00000385432.2

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

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.994

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.991

Alfa AF: 0.989 Hom.: 8678

Bravo AF: 0.977

Asia WGS AF: 0.996 AC: 3461 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 04, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.0
DANN	Benign	0.51

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: rs329297; hg19: chr5-133943857;