11-18245480-C-T

Variant names:

• chr11-18245480-C-T
• rs2468844
• NM_030754.5:c.266G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030754.5(SAA2):​c.266G>A​(p.Arg89His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,613,990 control chromosomes in the GnomAD database, including 587,906 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.81 (50183 hom., cov: 33)
  • Exomes 𝑓: 0.86 (537723 hom.)
• Consequence: SAA2 NM_030754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.93
• Publications: 36 publications found

Genes affected

SAA2 (HGNC:10514): (serum amyloid A2) 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. [provided by RefSeq, Jul 2020]

SAA2-SAA4 (HGNC:39550): (SAA2-SAA4 readthrough) This locus represents naturally occurring read-through transcription between the neighboring serum amyloid A2 and serum amyloid A4 genes on chromosome 11. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.348477E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030754.5. 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
	SAA2	NM_030754.5	MANE Select	c.266G>A	p.Arg89His	missense	Exon 4 of 4	NP_110381.2	P0DJI9-1
	SAA2	NM_001385666.1		c.266G>A	p.Arg89His	missense	Exon 5 of 5	NP_001372595.1	P0DJI9-1
	SAA2	NM_001385668.1		c.127G>A	p.Val43Met	missense	Exon 3 of 3	NP_001372597.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA2	ENST00000256733.9	TSL:1 MANE Select	c.266G>A	p.Arg89His	missense	Exon 4 of 4	ENSP00000256733.5	P0DJI9-1
	SAA2-SAA4	ENST00000524555.3	TSL:3	c.230+430G>A		intron	N/A	ENSP00000485552.1	A0A096LPE2
	SAA2	ENST00000414546.6	TSL:1	c.230+430G>A		intron	N/A	ENSP00000416716.2	P0DJI9-2

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122483 AN: 152070 Hom.: 50148 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.801

GnomAD2 exomes AF: 0.835 AC: 209909 AN: 251272 AF XY: 0.837

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.770

Gnomad ASJ exome AF: 0.839

Gnomad EAS exome AF: 0.941

Gnomad FIN exome AF: 0.930

Gnomad NFE exome AF: 0.871

Gnomad OTH exome AF: 0.831

GnomAD4 exome AF: 0.856 AC: 1251130 AN: 1461802 Hom.: 537723 Cov.: 60 AF XY: 0.854 AC XY: 620790 AN XY: 727204

African (AFR) AF: 0.641 AC: 21460 AN: 33472

American (AMR) AF: 0.772 AC: 34535 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 22025 AN: 26136

East Asian (EAS) AF: 0.915 AC: 36324 AN: 39700

South Asian (SAS) AF: 0.747 AC: 64432 AN: 86258

European-Finnish (FIN) AF: 0.923 AC: 49289 AN: 53418

Middle Eastern (MID) AF: 0.754 AC: 4348 AN: 5764

European-Non Finnish (NFE) AF: 0.871 AC: 968346 AN: 1111946

Other (OTH) AF: 0.834 AC: 50371 AN: 60388

GnomAD4 genome AF: 0.805 AC: 122570 AN: 152188 Hom.: 50183 Cov.: 33 AF XY: 0.809 AC XY: 60219 AN XY: 74426

African (AFR) AF: 0.655 AC: 27172 AN: 41470

American (AMR) AF: 0.806 AC: 12343 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2948 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4825 AN: 5170

South Asian (SAS) AF: 0.738 AC: 3558 AN: 4822

European-Finnish (FIN) AF: 0.936 AC: 9941 AN: 10620

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.869 AC: 59122 AN: 68010

Other (OTH) AF: 0.801 AC: 1694 AN: 2116

Alfa AF: 0.849 Hom.: 217558

Bravo AF: 0.792

TwinsUK AF: 0.885 AC: 3283

ALSPAC AF: 0.870 AC: 3352

ESP6500AA AF: 0.683 AC: 3004

ESP6500EA AF: 0.860 AC: 7382

ExAC AF: 0.831 AC: 100920

Asia WGS AF: 0.766 AC: 2666 AN: 3478

EpiCase AF: 0.860

EpiControl AF: 0.863

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.039
DANN	Benign	0.74
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.045	T
MetaRNN	Benign	8.3e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.49	N
PhyloP100		-3.9
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.061
Sift	Benign	0.52	T
Sift4G	Benign	0.34	T
Vest4		0.0060
MPC		0.021
ClinPred		0.026	T
GERP RS		-10
Varity_R		0.022
gMVP		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs2468844; hg19: chr11-18267027; COSMIC: COSV107218171; COSMIC: COSV107218171;