rs16935244

Variant names:

• chr11-18244739-T-C
• rs16935244
• ENST00000524555.3:c.230+1171A>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+1171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 152,234 control chromosomes in the GnomAD database, including 252 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 0.031 (252 hom., cov: 33)
• Consequence: SAA2-SAA4 ENST00000524555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA2-SAA4	NM_001199744.2	c.230+1171A>G		intron_variant	Intron 3 of 5		NP_001186673.1
SAA2	NM_001127380.3	c.230+1171A>G		intron_variant	Intron 3 of 3		NP_001120852.1
SAA2	NM_001385667.1	c.230+1171A>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+1171A>G		intron_variant	Intron 3 of 5	3		ENSP00000485552.1
SAA2	ENST00000414546.6	c.230+1171A>G		intron_variant	Intron 3 of 3	1		ENSP00000416716.2
SAA2	ENST00000528349.5	c.230+1171A>G		intron_variant	Intron 3 of 3	2		ENSP00000435659.1
SAA2	ENST00000530400.5	c.230+1171A>G		intron_variant	Intron 2 of 2	3		ENSP00000432370.1

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4695 AN: 152116 Hom.: 253 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0248

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

GnomAD4 genome AF: 0.0309 AC: 4698 AN: 152234 Hom.: 252 Cov.: 33 AF XY: 0.0299 AC XY: 2224 AN XY: 74426

African (AFR) AF: 0.107 AC: 4425 AN: 41502

American (AMR) AF: 0.0118 AC: 180 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68020

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.0395 Hom.: 187

Bravo AF: 0.0361

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.72
PhyloP100		-0.037
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: rs16935244; hg19: chr11-18266286;