rs11024595

Positions:

• chr11-18266251-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 11-18266251-C-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 153,192 control chromosomes in the GnomAD database, including 640 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (638 hom., cov: 29)
  • Exomes 𝑓: 0.045 (2 hom.)
• Consequence: SAA1 NM_199161.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAA1	NM_199161.5			upstream_gene_variant		ENST00000356524.9	NP_954630.2
SAA1	NM_000331.6			upstream_gene_variant			NP_000322.3
SAA1	NM_001178006.3			upstream_gene_variant			NP_001171477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAA1	ENST00000356524.9			upstream_gene_variant		1	NM_199161.5	ENSP00000348918	P1

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9628 AN: 152168 Hom.: 636 Cov.: 29

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0627

Gnomad ASJ AF: 0.0763

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0466

Gnomad OTH AF: 0.0555

GnomAD4 exome AF: 0.0453 AC: 41 AN: 906 Hom.: 2 Cov.: 0 AF XY: 0.0444 AC XY: 20 AN XY: 450

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0781

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.0750

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0359

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0634 AC: 9651 AN: 152286 Hom.: 638 Cov.: 29 AF XY: 0.0697 AC XY: 5193 AN XY: 74470

Gnomad4 AFR AF: 0.0285

Gnomad4 AMR AF: 0.0627

Gnomad4 ASJ AF: 0.0763

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0466

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0477 Hom.: 59

Bravo AF: 0.0616

Asia WGS AF: 0.265 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.72
DANN	Benign	0.63

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: rs11024595; hg19: chr11-18287798;