NM_199161.5:c.-50C>T

Variant names:

• chr11-18266251-C-T
• rs11024595
• NM_199161.5:c.-50C>T

Variant summary

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

The NM_199161.5(SAA1):​c.-50C>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
• Publications: 11 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]

RNA5SP334 (HGNC:43234): (RNA, 5S ribosomal pseudogene 334)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	NM_199161.5	MANE Select	c.-50C>T		upstream_gene	N/A	NP_954630.2
	SAA1	NM_000331.6		c.-197C>T		upstream_gene	N/A	NP_000322.3
	SAA1	NM_001178006.3		c.-111C>T		upstream_gene	N/A	NP_001171477.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	ENST00000356524.9	TSL:1 MANE Select	c.-50C>T		upstream_gene	N/A	ENSP00000348918.4
	SAA1	ENST00000532858.5	TSL:1	c.-111C>T		upstream_gene	N/A	ENSP00000436866.1
	SAA1	ENST00000405158.2	TSL:5	c.-197C>T		upstream_gene	N/A	ENSP00000384906.2

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.0781 AC: 10 AN: 128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.0750 AC: 3 AN: 40

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0359 AC: 25 AN: 696

Other (OTH) AF: 0.0625 AC: 2 AN: 32

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

African (AFR) AF: 0.0285 AC: 1184 AN: 41562

American (AMR) AF: 0.0627 AC: 960 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0763 AC: 265 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1990 AN: 5180

South Asian (SAS) AF: 0.132 AC: 635 AN: 4824

European-Finnish (FIN) AF: 0.121 AC: 1284 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0466 AC: 3170 AN: 68022

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0446 Hom.: 90

Bravo AF: 0.0616

Asia WGS AF: 0.265 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.72
DANN	Benign	0.63
PhyloP100		-1.2
PromoterAI		-0.055	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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: rs11024595; hg19: chr11-18287798;