rs2811226

Variant names:

• chr9-73169348-G-A
• rs2811226
• NM_000700.3:c.984+194G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000700.3(ANXA1):​c.984+194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,954 control chromosomes in the GnomAD database, including 36,738 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36738 hom., cov: 32)
• Consequence: ANXA1 NM_000700.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 8 publications found

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]

ENSG00000293607 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA1	NM_000700.3	c.984+194G>A		intron_variant	Intron 12 of 12	ENST00000257497.11	NP_000691.1
ANXA1	XM_017014657.2	c.1017+194G>A		intron_variant	Intron 12 of 12		XP_016870146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA1	ENST00000257497.11	c.984+194G>A		intron_variant	Intron 12 of 12	1	NM_000700.3	ENSP00000257497.6

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104476 AN: 151836 Hom.: 36694 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.677

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.688 AC: 104576 AN: 151954 Hom.: 36738 Cov.: 32 AF XY: 0.684 AC XY: 50818 AN XY: 74256

African (AFR) AF: 0.808 AC: 33509 AN: 41488

American (AMR) AF: 0.642 AC: 9778 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2246 AN: 3466

East Asian (EAS) AF: 0.309 AC: 1597 AN: 5160

South Asian (SAS) AF: 0.462 AC: 2225 AN: 4814

European-Finnish (FIN) AF: 0.706 AC: 7448 AN: 10554

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45461 AN: 67914

Other (OTH) AF: 0.672 AC: 1421 AN: 2116

Alfa AF: 0.666 Hom.: 41189

Bravo AF: 0.689

Asia WGS AF: 0.425 AC: 1474 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2811226; hg19: chr9-75784264; COSMIC: COSV57411729; COSMIC: COSV57411729;