1-153360788-G-A

Variant names:

• chr1-153360788-G-A
• rs143906646
• NM_002965.4:c.295G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002965.4(S100A9):​c.295G>A​(p.Glu99Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,613,764 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (7 hom.)
• Consequence: S100A9 NM_002965.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.56

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033789277).
• BP6: Variant 1-153360788-G-A is Benign according to our data. Variant chr1-153360788-G-A is described in ClinVar as [Benign]. Clinvar id is 732029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000716 (109/152324) while in subpopulation EAS AF= 0.0188 (97/5172). AF 95% confidence interval is 0.0157. There are 1 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A9	NM_002965.4	c.295G>A	p.Glu99Lys	missense_variant	Exon 3 of 3	ENST00000368738.4	NP_002956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A9	ENST00000368738.4	c.295G>A	p.Glu99Lys	missense_variant	Exon 3 of 3	1	NM_002965.4	ENSP00000357727.3

Frequencies

GnomAD3 genomes AF: 0.000716 AC: 109 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00152 AC: 381 AN: 249922 Hom.: 4 AF XY: 0.00146 AC XY: 198 AN XY: 135264

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.000598

Gnomad EAS exome AF: 0.0189

Gnomad SAS exome AF: 0.000689

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000529 AC: 773 AN: 1461440 Hom.: 7 Cov.: 31 AF XY: 0.000509 AC XY: 370 AN XY: 727010

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.000345

Gnomad4 EAS exome AF: 0.0159

Gnomad4 SAS exome AF: 0.000801

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.000613

GnomAD4 genome AF: 0.000716 AC: 109 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74494

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0188

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000883 Hom.: 4

Bravo AF: 0.000782

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00159 AC: 193

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.69
DANN	Benign	0.21
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.015
Sift	Benign	0.70	T
Sift4G	Benign	0.84	T
Polyphen		0.015	B
Vest4		0.16
MVP		0.21
MPC		0.55
ClinPred		0.0075	T
GERP RS		2.9
Varity_R		0.18
gMVP		0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs143906646; hg19: chr1-153333264;