dbSNP rs140163350: S100A9:c.151-5C>T (chr1-153360639-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002965.4(S100A9):c.151-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000922 in 1,595,394 control chromosomes in the GnomAD database, including 10 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 0.0043 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 4 hom. )

Consequence

S100A9
NM_002965.4 splice_region, intron

Scores

Splicing: ADA: 0.00001352

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.686

Publications

0 publications found

Variant links:

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]

S100A9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-153360639-C-T is Benign according to our data. Variant chr1-153360639-C-T is described in ClinVar as Benign. ClinVar VariationId is 789941.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002965.4. 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
	S100A9	NM_002965.4	MANE Select	c.151-5C>T		splice_region intron	N/A	NP_002956.1	P06702

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
S100A9	ENST00000368738.4	TSL:1 MANE Select	c.151-5C>T	splice_region intron	N/A	ENSP00000357727.3	P06702
S100A9	ENST00000872632.1		c.151-5C>T	splice_region intron	N/A	ENSP00000542691.1
S100A9	ENST00000872634.1		c.151-5C>T	splice_region intron	N/A	ENSP00000542693.1

Frequencies

GnomAD3 genomes

AF:

0.00432

AC:

657

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00129

AC:

310

AN:

240042

AF XY:

0.000907

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000859

GnomAD4 exome

AF:

0.000564

AC:

814

AN:

1443116

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

365

AN XY:

715722

show subpopulations

African (AFR)

AF:

0.0147

AC:

487

AN:

33100

American (AMR)

AF:

0.00162

AC:

AN:

43870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25418

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39114

South Asian (SAS)

AF:

0.000236

AC:

AN:

84614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52938

Middle Eastern (MID)

AF:

0.00176

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.000120

AC:

132

AN:

1098796

Other (OTH)

AF:

0.00156

AC:

AN:

59568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00431

AC:

657

AN:

152278

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

315

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0139

AC:

579

AN:

41554

American (AMR)

AF:

0.00340

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68018

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00483

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.41

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0060

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over