11-18269832-G-C

Variant names:

• chr11-18269832-G-C
• rs1416698471
• NM_199161.5:c.346G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_199161.5(SAA1):​c.346G>C​(p.Ala116Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SAA1 NM_199161.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06630227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA1	NM_199161.5	c.346G>C	p.Ala116Pro	missense_variant	Exon 4 of 4	ENST00000356524.9	NP_954630.2
SAA1	NM_000331.6	c.346G>C	p.Ala116Pro	missense_variant	Exon 4 of 4		NP_000322.3
SAA1	NM_001178006.3	c.346G>C	p.Ala116Pro	missense_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.346G>C	p.Ala116Pro	missense_variant	Exon 4 of 4	1	NM_199161.5	ENSP00000348918.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251432 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.3
DANN	Benign	0.78
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.52	.;.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Benign	0.051
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.30	T;T;T
Vest4		0.18
MutPred		0.36		Gain of catalytic residue at P115 (P = 0.0164);Gain of catalytic residue at P115 (P = 0.0164);Gain of catalytic residue at P115 (P = 0.0164);
MVP		0.030
MPC		0.0077
ClinPred		0.37	T
GERP RS		-4.1
gMVP		0.22

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: rs1416698471; hg19: chr11-18291379;