chr11-18246450-A-T

Position:

• chr11-18246450-A-T

Variant summary

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

The NM_030754.5(SAA2):​c.92-402T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,174 control chromosomes in the GnomAD database, including 11,683 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 0.37 (11683 hom., cov: 33)
• Consequence: SAA2 NM_030754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAA2	NM_030754.5	c.92-402T>A		intron_variant		ENST00000256733.9	NP_110381.2
SAA2-SAA4	NM_001199744.2	c.92-402T>A		intron_variant			NP_001186673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAA2	ENST00000256733.9	c.92-402T>A		intron_variant		1	NM_030754.5	ENSP00000256733	P1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56115 AN: 152056 Hom.: 11680 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.369 AC: 56146 AN: 152174 Hom.: 11683 Cov.: 33 AF XY: 0.373 AC XY: 27779 AN XY: 74394

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.0376

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.364

Alfa AF: 0.413 Hom.: 1855

Bravo AF: 0.340

Asia WGS AF: 0.190 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.53

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: rs7113375; hg19: chr11-18267997;