11-18269319-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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.

• 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

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 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=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.185 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA1	NM_199161.5	c.216T>G	p.Ala72Ala	synonymous_variant	Exon 3 of 4	ENST00000356524.9	NP_954630.2
SAA1	NM_000331.6	c.216T>G	p.Ala72Ala	synonymous_variant	Exon 3 of 4		NP_000322.3
SAA1	NM_001178006.3	c.216T>G	p.Ala72Ala	synonymous_variant	Exon 4 of 5		NP_001171477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAA1	ENST00000356524.9	c.216T>G	p.Ala72Ala	synonymous_variant	Exon 3 of 4	1	NM_199161.5	ENSP00000348918.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000286

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18290866;