11-18244252-C-T

Variant names:

• chr11-18244252-C-T
• rs12282742
• ENST00000524555.3:c.230+1658G>A

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+1658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 152,312 control chromosomes in the GnomAD database, including 269 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 0.046 (269 hom., cov: 32)
• Consequence: SAA2-SAA4 ENST00000524555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 9 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 (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA2-SAA4	NM_001199744.2	c.230+1658G>A		intron_variant	Intron 3 of 5		NP_001186673.1
SAA2	NM_001127380.3	c.230+1658G>A		intron_variant	Intron 3 of 3		NP_001120852.1
SAA2	NM_001385667.1	c.230+1658G>A		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+1658G>A		intron_variant	Intron 3 of 5	3		ENSP00000485552.1
SAA2	ENST00000414546.6	c.230+1658G>A		intron_variant	Intron 3 of 3	1		ENSP00000416716.2
SAA2	ENST00000528349.5	c.231-1433G>A		intron_variant	Intron 3 of 3	2		ENSP00000435659.1
SAA2	ENST00000530400.5	c.230+1658G>A		intron_variant	Intron 2 of 2	3		ENSP00000432370.1

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 7008 AN: 152194 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0830

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0466

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0461 AC: 7020 AN: 152312 Hom.: 269 Cov.: 32 AF XY: 0.0485 AC XY: 3615 AN XY: 74478

African (AFR) AF: 0.0146 AC: 605 AN: 41566

American (AMR) AF: 0.110 AC: 1678 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.0832 AC: 432 AN: 5190

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4826

European-Finnish (FIN) AF: 0.0620 AC: 658 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0467 AC: 3175 AN: 68028

Other (OTH) AF: 0.0520 AC: 110 AN: 2116

Alfa AF: 0.0485 Hom.: 519

Bravo AF: 0.0515

Asia WGS AF: 0.0440 AC: 155 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	0.91
DANN	Benign	0.37
PhyloP100		-0.35
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: rs12282742; hg19: chr11-18265799;