Variant chr11-18269190-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199161.5(SAA1):c.92-5T>G variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0009551

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.11

Variant links:

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]

SAA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SAA1	NM_199161.5 linkuse as main transcript	c.92-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000356524.9
SAA1	NM_000331.6 linkuse as main transcript	c.92-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SAA1	NM_001178006.3 linkuse as main transcript	c.92-5T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAA1	ENST00000356524.9 linkuse as main transcript	c.92-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_199161.5	P1

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

78287

AN:

148192

Hom.:

16045

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.491

AC:

101929

AN:

207700

Hom.:

17177

AF XY:

0.491

AC XY:

55308

AN XY:

112670

show subpopulations

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 SAS exome

AF:

0.430

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.:

AF XY:

0.536

AC XY:

368801

AN XY:

688320

show subpopulations

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.378

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.572

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.512

GnomAD4 genome

AF:

0.528

AC:

78343

AN:

148320

Hom.:

16059

Cov.:

AF XY:

0.522

AC XY:

37872

AN XY:

72494

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.483

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.441

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.571

Gnomad4 OTH

AF:

0.484

Alfa

AF:

0.528

Hom.:

2766

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

DANN

Benign

0.81

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over