11-18269807-CAA-C

Variant names:

• chr11-18269807-CAA-C
• rs148453200
• NM_199161.5:c.323_324delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_199161.5(SAA1):​c.323_324delAA​(p.Lys108ArgfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,614,156 control chromosomes in the GnomAD database, including 30 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00098 (16 hom.)
• Consequence: SAA1 NM_199161.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.77

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: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-18269807-CAA-C is Benign according to our data. Variant chr11-18269807-CAA-C is described in ClinVar as [Benign]. Clinvar id is 787593.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00889 (1354/152318) while in subpopulation AFR AF = 0.0313 (1300/41564). AF 95% confidence interval is 0.0299. There are 14 homozygotes in GnomAd4. There are 622 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA1	NM_199161.5	c.323_324delAA	p.Lys108ArgfsTer12	frameshift_variant	Exon 4 of 4	ENST00000356524.9	NP_954630.2
SAA1	NM_000331.6	c.323_324delAA	p.Lys108ArgfsTer12	frameshift_variant	Exon 4 of 4		NP_000322.3
SAA1	NM_001178006.3	c.323_324delAA	p.Lys108ArgfsTer12	frameshift_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.323_324delAA	p.Lys108ArgfsTer12	frameshift_variant	Exon 4 of 4	1	NM_199161.5	ENSP00000348918.4

Frequencies

GnomAD3 genomes AF: 0.00891 AC: 1356 AN: 152200 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00239 AC: 602 AN: 251470 AF XY: 0.00187

Gnomad AFR exome AF: 0.0314

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000981 AC: 1434 AN: 1461838 Hom.: 16 AF XY: 0.000842 AC XY: 612 AN XY: 727224

Gnomad4 AFR exome AF: 0.0323 AC: 1080 AN: 33474

Gnomad4 AMR exome AF: 0.00190 AC: 85 AN: 44722

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26132

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000116 AC: 10 AN: 86254

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53420

Gnomad4 NFE exome AF: 0.000108 AC: 120 AN: 1111982

Gnomad4 Remaining exome AF: 0.00209 AC: 126 AN: 60386

GnomAD4 genome AF: 0.00889 AC: 1354 AN: 152318 Hom.: 14 Cov.: 33 AF XY: 0.00835 AC XY: 622 AN XY: 74480

Gnomad4 AFR AF: 0.0313 AC: 0.0312771 AN: 0.0312771

Gnomad4 AMR AF: 0.00190 AC: 0.00189518 AN: 0.00189518

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000206954 AN: 0.000206954

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000162 AC: 0.000161684 AN: 0.000161684

Gnomad4 OTH AF: 0.00521 AC: 0.00521327 AN: 0.00521327

Alfa AF: 0.00119 Hom.: 0

Bravo AF: 0.00988

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=193/7	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

Publications

LitVar

Other links and lift over

dbSNP: rs148453200; hg19: chr11-18291354;