chr11-18266901-C-T

Variant names:

• chr11-18266901-C-T
• rs372757378
• NM_199161.5:c.14C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_199161.5(SAA1):​c.14C>T​(p.Thr5Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,612,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: SAA1 NM_199161.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.112
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07746449).

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.14C>T	p.Thr5Met	missense	Exon 2 of 4	NP_954630.2	P0DJI8
	SAA1	NM_000331.6		c.14C>T	p.Thr5Met	missense	Exon 2 of 4	NP_000322.3
	SAA1	NM_001178006.3		c.14C>T	p.Thr5Met	missense	Exon 3 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.14C>T	p.Thr5Met	missense	Exon 2 of 4	ENSP00000348918.4	P0DJI8
	SAA1	ENST00000532858.5	TSL:1	c.14C>T	p.Thr5Met	missense	Exon 3 of 5	ENSP00000436866.1	P0DJI8
	SAA1	ENST00000405158.2	TSL:5	c.14C>T	p.Thr5Met	missense	Exon 2 of 4	ENSP00000384906.2	P0DJI8

Frequencies

GnomAD3 genomes AF: 0.000252 AC: 38 AN: 151022 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000661

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000464

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000966

GnomAD2 exomes AF: 0.0000876 AC: 22 AN: 251132 AF XY: 0.0000589

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461356 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 727006

African (AFR) AF: 0.000837 AC: 28 AN: 33456

American (AMR) AF: 0.000358 AC: 16 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111734

Other (OTH) AF: 0.0000331 AC: 2 AN: 60358

GnomAD4 genome AF: 0.000251 AC: 38 AN: 151138 Hom.: 0 Cov.: 23 AF XY: 0.000271 AC XY: 20 AN XY: 73814

African (AFR) AF: 0.000659 AC: 27 AN: 40950

American (AMR) AF: 0.000463 AC: 7 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5134

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67916

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.11
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.11
Sift	Benign	0.061	T
Sift4G	Benign	0.13	T
Vest4		0.54
MVP		0.20
MPC		1.8
ClinPred		0.025	T
GERP RS		2.8
gMVP		0.48
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs372757378; hg19: chr11-18288448;