chr11-18243537-G-C

Variant names:

• chr11-18243537-G-C
• rs2460824
• ENST00000524555.3:c.230+2373C>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+2373C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,240 control chromosomes in the GnomAD database, including 64,522 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 0.92 (64522 hom., cov: 31)
• Consequence: SAA2-SAA4 ENST00000524555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA2-SAA4	NM_001199744.2	c.230+2373C>G		intron_variant	Intron 3 of 5		NP_001186673.1
SAA2	NM_001127380.3	c.230+2373C>G		intron_variant	Intron 3 of 3		NP_001120852.1
SAA2	NM_001385667.1	c.230+2373C>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+2373C>G		intron_variant	Intron 3 of 5	3		ENSP00000485552.1
SAA2	ENST00000414546.6	c.230+2373C>G		intron_variant	Intron 3 of 3	1		ENSP00000416716.2
SAA2	ENST00000528349.5	c.231-718C>G		intron_variant	Intron 3 of 3	2		ENSP00000435659.1
SAA2	ENST00000530400.5	c.230+2373C>G		intron_variant	Intron 2 of 2	3		ENSP00000432370.1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139920 AN: 152122 Hom.: 64477 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.920 AC: 140022 AN: 152240 Hom.: 64522 Cov.: 31 AF XY: 0.921 AC XY: 68536 AN XY: 74430

African (AFR) AF: 0.875 AC: 36325 AN: 41524

American (AMR) AF: 0.886 AC: 13547 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3310 AN: 3470

East Asian (EAS) AF: 0.932 AC: 4829 AN: 5180

South Asian (SAS) AF: 0.904 AC: 4365 AN: 4826

European-Finnish (FIN) AF: 0.976 AC: 10369 AN: 10620

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.944 AC: 64216 AN: 68010

Other (OTH) AF: 0.923 AC: 1953 AN: 2116

Alfa AF: 0.934 Hom.: 2202

Bravo AF: 0.910

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.47
PhyloP100		-0.15
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: rs2460824; hg19: chr11-18265084;