rs140163350

Variant names:

• chr1-153360639-C-A
• rs140163350
• NM_002965.4:c.151-5C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-153360639-C-A
• chr1-153360639-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002965.4(S100A9):​c.151-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,443,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: S100A9 NM_002965.4 splice_region, intron
• Scores: Splicing: ADA: 0.9446
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

Genes affected

S100A9 (HGNC:10499): (S100 calcium binding protein A9) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in the inhibition of casein kinase and altered expression of this protein is associated with the disease cystic fibrosis. This antimicrobial protein exhibits antifungal and antibacterial activity. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A9	NM_002965.4	c.151-5C>A		splice_region_variant, intron_variant	Intron 2 of 2	ENST00000368738.4	NP_002956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A9	ENST00000368738.4	c.151-5C>A		splice_region_variant, intron_variant	Intron 2 of 2	1	NM_002965.4	ENSP00000357727.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000417 AC: 1 AN: 240042 Hom.: 0 AF XY: 0.00000768 AC XY: 1 AN XY: 130144

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000926

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1443126 Hom.: 0 Cov.: 29 AF XY: 0.00000279 AC XY: 2 AN XY: 715726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000273

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	19
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.94
dbscSNV1_RF	Pathogenic	0.80
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.97		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs140163350; hg19: chr1-153333115;