chr11-18269807-C-CAA

Variant names:

• chr11-18269807-C-CAA
• rs148453200
• NM_199161.5:c.323_324dupAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_199161.5(SAA1):​c.323_324dupAA​(p.Asp109LysfsTer50) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAA1 NM_199161.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76

Genes affected

SAA1 (HGNC:10513): (serum amyloid A1) This gene encodes a member of the serum amyloid A family of apolipoproteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a major acute phase protein that is highly expressed in response to inflammation and tissue injury. This protein also plays an important role in HDL metabolism and cholesterol homeostasis. High levels of this protein are associated with chronic inflammatory diseases including atherosclerosis, rheumatoid arthritis, Alzheimer's disease and Crohn's disease. This protein may also be a potential biomarker for certain tumors. Finally, antimicrobial activity against S. aureus and E. coli resides in the N-terminal portion of the mature protein. Alternate splicing results in multiple transcript variants that encode the same protein. A pseudogene of this gene is found on chromosome 11. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA1	NM_199161.5	c.323_324dupAA	p.Asp109LysfsTer50	frameshift_variant	Exon 4 of 4	ENST00000356524.9	NP_954630.2
SAA1	NM_000331.6	c.323_324dupAA	p.Asp109LysfsTer50	frameshift_variant	Exon 4 of 4		NP_000322.3
SAA1	NM_001178006.3	c.323_324dupAA	p.Asp109LysfsTer50	frameshift_variant	Exon 5 of 5		NP_001171477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAA1	ENST00000356524.9	c.323_324dupAA	p.Asp109LysfsTer50	frameshift_variant	Exon 4 of 4	1	NM_199161.5	ENSP00000348918.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs148453200; hg19: chr11-18291354;