11-18246450-A-T

Variant names:

• chr11-18246450-A-T
• rs7113375
• NM_030754.5:c.92-402T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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:39550): (SAA2-SAA4 readthrough) This locus represents naturally occurring read-through transcription between the neighboring serum amyloid A2 and serum amyloid A4 genes on chromosome 11. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SAA2	NM_030754.5	c.92-402T>A		intron_variant	Intron 2 of 3	ENST00000256733.9	NP_110381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAA2	ENST00000256733.9	c.92-402T>A		intron_variant	Intron 2 of 3	1	NM_030754.5	ENSP00000256733.5
SAA2-SAA4	ENST00000524555.3	c.92-402T>A		intron_variant	Intron 2 of 5	3		ENSP00000485552.1

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

African (AFR) AF: 0.219 AC: 9108 AN: 41516

American (AMR) AF: 0.348 AC: 5319 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3470

East Asian (EAS) AF: 0.0376 AC: 195 AN: 5188

South Asian (SAS) AF: 0.352 AC: 1698 AN: 4824

European-Finnish (FIN) AF: 0.582 AC: 6153 AN: 10576

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30882 AN: 67992

Other (OTH) AF: 0.364 AC: 771 AN: 2116

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
PhyloP100		-0.37
Mutation Taster		=100/0	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: rs7113375; hg19: chr11-18267997;