11-18243024-T-C

Variant names:

• chr11-18243024-T-C
• rs1520887
• ENST00000524555.3:c.230+2886A>G

Variant summary

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

The ENST00000524555.3(SAA2-SAA4):​c.230+2886A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,078 control chromosomes in the GnomAD database, including 8,105 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 0.31 (8105 hom., cov: 32)
• Consequence: SAA2-SAA4 ENST00000524555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 3 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA2-SAA4	NM_001199744.2	c.230+2886A>G		intron_variant	Intron 3 of 5		NP_001186673.1
SAA2	NM_001127380.3	c.230+2886A>G		intron_variant	Intron 3 of 3		NP_001120852.1
SAA2	NM_001385667.1	c.230+2886A>G		intron_variant	Intron 4 of 4		NP_001372596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAA2-SAA4	ENST00000524555.3	c.230+2886A>G		intron_variant	Intron 3 of 5	3		ENSP00000485552.1
SAA2	ENST00000414546.6	c.230+2886A>G		intron_variant	Intron 3 of 3	1		ENSP00000416716.2
SAA2	ENST00000528349.5	c.231-205A>G		intron_variant	Intron 3 of 3	2		ENSP00000435659.1
SAA2	ENST00000530400.5	c.231-2737A>G		intron_variant	Intron 2 of 2	3		ENSP00000432370.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46551 AN: 151962 Hom.: 8081 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.307 AC: 46627 AN: 152078 Hom.: 8105 Cov.: 32 AF XY: 0.299 AC XY: 22254 AN XY: 74330

African (AFR) AF: 0.474 AC: 19657 AN: 41466

American (AMR) AF: 0.289 AC: 4413 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3468

East Asian (EAS) AF: 0.360 AC: 1865 AN: 5176

South Asian (SAS) AF: 0.163 AC: 784 AN: 4814

European-Finnish (FIN) AF: 0.162 AC: 1720 AN: 10594

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16132 AN: 67954

Other (OTH) AF: 0.319 AC: 674 AN: 2112

Alfa AF: 0.254 Hom.: 8771

Bravo AF: 0.327

Asia WGS AF: 0.284 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.9
DANN	Benign	0.56
PhyloP100		1.0
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: rs1520887; hg19: chr11-18264571;