11-18269319-T-G

Variant names:

• chr11-18269319-T-G
• rs1136745
• NM_199161.5:c.216T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_199161.5(SAA1):​c.216T>G​(p.Ala72Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,313,660 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. Synonymous variant affecting the same amino acid position (i.e. A72A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: SAA1 NM_199161.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.185 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199161.5. 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
	SAA1	NM_199161.5	MANE Select	c.216T>G	p.Ala72Ala	synonymous	Exon 3 of 4	NP_954630.2	P0DJI8
	SAA1	NM_000331.6		c.216T>G	p.Ala72Ala	synonymous	Exon 3 of 4	NP_000322.3
	SAA1	NM_001178006.3		c.216T>G	p.Ala72Ala	synonymous	Exon 4 of 5	NP_001171477.2	P0DJI8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	ENST00000356524.9	TSL:1 MANE Select	c.216T>G	p.Ala72Ala	synonymous	Exon 3 of 4	ENSP00000348918.4	P0DJI8
	SAA1	ENST00000532858.5	TSL:1	c.216T>G	p.Ala72Ala	synonymous	Exon 4 of 5	ENSP00000436866.1	P0DJI8
	SAA1	ENST00000405158.2	TSL:5	c.216T>G	p.Ala72Ala	synonymous	Exon 3 of 4	ENSP00000384906.2	P0DJI8

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.61e-7 AC: 1 AN: 1313660 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 642862

African (AFR) AF: 0.00 AC: 0 AN: 28922

American (AMR) AF: 0.00 AC: 0 AN: 25664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20146

East Asian (EAS) AF: 0.0000286 AC: 1 AN: 35012

South Asian (SAS) AF: 0.00 AC: 0 AN: 67444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5078

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029546

Other (OTH) AF: 0.00 AC: 0 AN: 54096

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.34
PhyloP100		-0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1136745; hg19: chr11-18290866;