dbSNP rs3739956: ANXA1:c.-17A>G (chr9-73151922-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000700.3(ANXA1):c.-17A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 152,232 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.068 ( 417 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

ANXA1
NM_000700.3 splice_region

Scores

Splicing: ADA: 0.00004733

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.404

Publications

4 publications found

Variant links:

Genes affected

ANXA1 (HGNC:533): (annexin A1) This gene encodes a membrane-localized protein that binds phospholipids. This protein inhibits phospholipase A2 and has anti-inflammatory activity. Loss of function or expression of this gene has been detected in multiple tumors. [provided by RefSeq, Dec 2014]

ANXA1 links:

ENSG00000293607 (HGNC:):

ENSG00000293607 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000700.3. 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
	ANXA1	NM_000700.3	MANE Select	c.-17A>G		splice_region	Exon 1 of 13	NP_000691.1	Q5TZZ9
	ANXA1	NM_000700.3	MANE Select	c.-17A>G		5_prime_UTR	Exon 1 of 13	NP_000691.1	Q5TZZ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANXA1	ENST00000257497.11	TSL:1 MANE Select	c.-17A>G	splice_region	Exon 1 of 13	ENSP00000257497.6	P04083
ANXA1	ENST00000257497.11	TSL:1 MANE Select	c.-17A>G	5_prime_UTR	Exon 1 of 13	ENSP00000257497.6	P04083
ANXA1	ENST00000857790.1		c.-138A>G	splice_region	Exon 1 of 14	ENSP00000527849.1

Frequencies

GnomAD3 genomes

AF:

0.0685

AC:

10420

AN:

152114

Hom.:

416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0531

Gnomad ASJ

AF:

0.0788

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.0518

Gnomad FIN

AF:

0.0321

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0412

Gnomad OTH

AF:

0.0666

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0685

AC:

10423

AN:

152232

Hom.:

417

Cov.:

AF XY:

0.0681

AC XY:

5067

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.119

AC:

4921

AN:

41522

American (AMR)

AF:

0.0531

AC:

812

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0788

AC:

273

AN:

3466

East Asian (EAS)

AF:

0.163

AC:

840

AN:

5164

South Asian (SAS)

AF:

0.0514

AC:

248

AN:

4824

European-Finnish (FIN)

AF:

0.0321

AC:

341

AN:

10618

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0412

AC:

2804

AN:

68020

Other (OTH)

AF:

0.0649

AC:

137

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

493

986

1480

1973

2466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0574

Hom.:

Bravo

AF:

0.0757

Asia WGS

AF:

0.103

AC:

358

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.2

(source)

DANN

Benign

0.74

PhyloP100

0.40

PromoterAI

-0.073

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.0020

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over