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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANXA1	NM_000700.3 link	c.-17A>G	splice_region_variant	Exon 1 of 13	ENST00000257497.11	NP_000691.1	P04083Q5TZZ9
ANXA1	NM_000700.3 link	c.-17A>G	5_prime_UTR_variant	Exon 1 of 13	ENST00000257497.11	NP_000691.1	P04083Q5TZZ9
ANXA1	XM_017014657.2 link	c.-2402A>G	5_prime_UTR_variant	Exon 1 of 13		XP_016870146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA1	ENST00000257497.11 link	c.-17A>G		splice_region_variant	Exon 1 of 13	1	NM_000700.3	ENSP00000257497.6		P04083
ANXA1	ENST00000257497.11 link	c.-17A>G		5_prime_UTR_variant	Exon 1 of 13	1	NM_000700.3	ENSP00000257497.6		P04083

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over