rs757598085

Variant names:

• chr11-116790227-G-C
• NM_001371904.1:c.1002C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-116790227-G-C
• chr11-116790227-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001371904.1(APOA5):​c.1002C>G​(p.Gly334Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOA5 NM_001371904.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

Genes affected

APOA5 (HGNC:17288): (apolipoprotein A5) The protein encoded by this gene is an apolipoprotein that plays an important role in regulating the plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5. This gene is located proximal to the apolipoprotein gene cluster on chromosome 11q23. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=0.071 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA5	NM_001371904.1	c.1002C>G	p.Gly334Gly	synonymous_variant	Exon 3 of 3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2	c.1002C>G	p.Gly334Gly	synonymous_variant	Exon 4 of 4		NP_001160070.1
APOA5	NM_052968.5	c.1002C>G	p.Gly334Gly	synonymous_variant	Exon 4 of 4		NP_443200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA5	ENST00000227665.9	c.1002C>G	p.Gly334Gly	synonymous_variant	Exon 3 of 3	1	NM_001371904.1	ENSP00000227665.4
APOA5	ENST00000433069.2	c.1002C>G	p.Gly334Gly	synonymous_variant	Exon 4 of 4	1		ENSP00000399701.2
APOA5	ENST00000673688.1	c.1086C>G	p.Gly362Gly	synonymous_variant	Exon 3 of 3			ENSP00000501141.1
APOA5	ENST00000542499.5	c.1002C>G	p.Gly334Gly	synonymous_variant	Exon 4 of 4	5		ENSP00000445002.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-116660943;