chr11-18269809-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_199161.5(SAA1):ā€‹c.323A>Gā€‹(p.Lys108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,608,608 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.0099 ( 5 hom., cov: 33)
Exomes š‘“: 0.013 ( 145 hom. )

Consequence

SAA1
NM_199161.5 missense

Scores

16

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.77
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009404242).
BP6
Variant 11-18269809-A-G is Benign according to our data. Variant chr11-18269809-A-G is described in ClinVar as [Benign]. Clinvar id is 3387956.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SAA1NM_199161.5 linkuse as main transcriptc.323A>G p.Lys108Arg missense_variant 4/4 ENST00000356524.9 NP_954630.2 P0DJI8
SAA1NM_000331.6 linkuse as main transcriptc.323A>G p.Lys108Arg missense_variant 4/4 NP_000322.3 P0DJI8
SAA1NM_001178006.3 linkuse as main transcriptc.323A>G p.Lys108Arg missense_variant 5/5 NP_001171477.2 P0DJI8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SAA1ENST00000356524.9 linkuse as main transcriptc.323A>G p.Lys108Arg missense_variant 4/41 NM_199161.5 ENSP00000348918.4 P0DJI8

Frequencies

GnomAD3 genomes
AF:
0.00997
AC:
1490
AN:
149496
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00337
Gnomad AMI
AF:
0.0362
Gnomad AMR
AF:
0.0111
Gnomad ASJ
AF:
0.0164
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.00744
Gnomad MID
AF:
0.00321
Gnomad NFE
AF:
0.0145
Gnomad OTH
AF:
0.0116
GnomAD3 exomes
AF:
0.0104
AC:
2622
AN:
251476
Hom.:
18
AF XY:
0.0102
AC XY:
1393
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00258
Gnomad AMR exome
AF:
0.00798
Gnomad ASJ exome
AF:
0.0158
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00209
Gnomad FIN exome
AF:
0.00850
Gnomad NFE exome
AF:
0.0160
Gnomad OTH exome
AF:
0.0129
GnomAD4 exome
AF:
0.0128
AC:
18619
AN:
1458990
Hom.:
145
Cov.:
35
AF XY:
0.0125
AC XY:
9106
AN XY:
726014
show subpopulations
Gnomad4 AFR exome
AF:
0.00201
Gnomad4 AMR exome
AF:
0.00884
Gnomad4 ASJ exome
AF:
0.0168
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00254
Gnomad4 FIN exome
AF:
0.00876
Gnomad4 NFE exome
AF:
0.0147
Gnomad4 OTH exome
AF:
0.0115
GnomAD4 genome
AF:
0.00995
AC:
1488
AN:
149618
Hom.:
5
Cov.:
33
AF XY:
0.00953
AC XY:
698
AN XY:
73224
show subpopulations
Gnomad4 AFR
AF:
0.00336
Gnomad4 AMR
AF:
0.0111
Gnomad4 ASJ
AF:
0.0164
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.00744
Gnomad4 NFE
AF:
0.0145
Gnomad4 OTH
AF:
0.0110
Alfa
AF:
0.0121
Hom.:
7
Bravo
AF:
0.0101
TwinsUK
AF:
0.0143
AC:
53
ALSPAC
AF:
0.0153
AC:
59
ExAC
AF:
0.0108
AC:
1308
EpiCase
AF:
0.0134
EpiControl
AF:
0.0148

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2024SAA1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.020
T;T;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.71
.;.;T
MetaRNN
Benign
0.0094
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.094
Sift
Benign
0.19
T;T;T
Sift4G
Benign
0.41
T;T;T
Vest4
0.069
MPC
0.0092
ClinPred
0.018
T
GERP RS
1.2
gMVP
0.31

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1059571; hg19: chr11-18291356; API