NM_199161.5:c.92-5T>G

Variant names:

• chr11-18269190-T-G
• rs11024597
• NM_199161.5:c.92-5T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_199161.5(SAA1):​c.92-5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 148,320 control chromosomes in the GnomAD database, including 16,059 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (16059 hom., cov: 31)
  • Exomes 𝑓: 0.54 (139647 hom.)
  • Failed GnomAD Quality Control
• Consequence: SAA1 NM_199161.5 splice_region, intron
• Scores: Splicing: ADA: 0.0009551
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.11
• Publications: 7 publications found

Genes affected

SAA1 (HGNC:10513): (serum amyloid A1) 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. Alternate splicing results in multiple transcript variants that encode the same protein. A pseudogene of this gene is found on chromosome 11. [provided by RefSeq, Jul 2020]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-18269190-T-G is Benign according to our data. Variant chr11-18269190-T-G is described in ClinVar as Benign. ClinVar VariationId is 768433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199161.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	NM_199161.5	MANE Select	c.92-5T>G		splice_region intron	N/A	NP_954630.2	P0DJI8
	SAA1	NM_000331.6		c.92-5T>G		splice_region intron	N/A	NP_000322.3
	SAA1	NM_001178006.3		c.92-5T>G		splice_region intron	N/A	NP_001171477.2	P0DJI8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	ENST00000356524.9	TSL:1 MANE Select	c.92-5T>G		splice_region intron	N/A	ENSP00000348918.4	P0DJI8
	SAA1	ENST00000532858.5	TSL:1	c.92-5T>G		splice_region intron	N/A	ENSP00000436866.1	P0DJI8
	SAA1	ENST00000405158.2	TSL:5	c.92-5T>G		splice_region intron	N/A	ENSP00000384906.2	P0DJI8

Frequencies

GnomAD3 genomes AF: 0.528 AC: 78287 AN: 148192 Hom.: 16045 Cov.: 31

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.487

GnomAD2 exomes AF: 0.491 AC: 101929 AN: 207700 AF XY: 0.491

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.436

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.263

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.547

Gnomad OTH exome AF: 0.498

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.540 AC: 748710 AN: 1385414 Hom.: 139647 Cov.: 43 AF XY: 0.536 AC XY: 368801 AN XY: 688320

African (AFR) AF: 0.498 AC: 15042 AN: 30234

American (AMR) AF: 0.440 AC: 13866 AN: 31484

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 8964 AN: 23738

East Asian (EAS) AF: 0.265 AC: 10360 AN: 39094

South Asian (SAS) AF: 0.426 AC: 33148 AN: 77782

European-Finnish (FIN) AF: 0.572 AC: 29582 AN: 51696

Middle Eastern (MID) AF: 0.342 AC: 1843 AN: 5384

European-Non Finnish (NFE) AF: 0.568 AC: 606549 AN: 1068640

Other (OTH) AF: 0.512 AC: 29356 AN: 57362

GnomAD4 genome AF: 0.528 AC: 78343 AN: 148320 Hom.: 16059 Cov.: 31 AF XY: 0.522 AC XY: 37872 AN XY: 72494

African (AFR) AF: 0.523 AC: 21245 AN: 40638

American (AMR) AF: 0.483 AC: 7162 AN: 14820

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1340 AN: 3402

East Asian (EAS) AF: 0.273 AC: 1398 AN: 5112

South Asian (SAS) AF: 0.441 AC: 2089 AN: 4732

European-Finnish (FIN) AF: 0.573 AC: 5903 AN: 10300

Middle Eastern (MID) AF: 0.344 AC: 99 AN: 288

European-Non Finnish (NFE) AF: 0.571 AC: 37726 AN: 66084

Other (OTH) AF: 0.484 AC: 989 AN: 2044

Alfa AF: 0.528 Hom.: 2766

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.81
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00096
dbscSNV1_RF	Benign	0.090
SpliceAI score (max)		0.15		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: rs11024597; hg19: chr11-18290737; COSMIC: COSV62946195; COSMIC: COSV62946195;