chr2-69790303-A-G

Variant names:

• chr2-69790303-A-G
• rs7577864
• NM_001153.5:c.97+2162A>G

Variant summary

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

The NM_001153.5(ANXA4):​c.97+2162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 150,650 control chromosomes in the GnomAD database, including 3,313 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 0.20 (3313 hom., cov: 31)
• Consequence: ANXA4 NM_001153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 3 publications found

Genes affected

ANXA4 (HGNC:542): (annexin A4) Annexin IV (ANX4) belongs to the annexin family of calcium-dependent phospholipid binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. ANX4 has 45 to 59% identity with other members of its family and shares a similar size and exon-intron organization. Isolated from human placenta, ANX4 encodes a protein that has possible interactions with ATP, and has in vitro anticoagulant activity and also inhibits phospholipase A2 activity. ANX4 is almost exclusively expressed in epithelial cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2016]

SMANTIS (HGNC:54417): (SMARCA4 interacting SWI/SNF chromatin remodeling complex scaffold lncRNA)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA4	NM_001153.5	c.97+2162A>G		intron_variant	Intron 3 of 12	ENST00000394295.6	NP_001144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA4	ENST00000394295.6	c.97+2162A>G		intron_variant	Intron 3 of 12	1	NM_001153.5	ENSP00000377833.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29526 AN: 150542 Hom.: 3311 Cov.: 31

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.216

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.196 AC: 29531 AN: 150650 Hom.: 3313 Cov.: 31 AF XY: 0.201 AC XY: 14824 AN XY: 73632

African (AFR) AF: 0.0813 AC: 3268 AN: 40204

American (AMR) AF: 0.226 AC: 3430 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3464

East Asian (EAS) AF: 0.330 AC: 1705 AN: 5160

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4808

European-Finnish (FIN) AF: 0.248 AC: 2622 AN: 10552

Middle Eastern (MID) AF: 0.226 AC: 65 AN: 288

European-Non Finnish (NFE) AF: 0.228 AC: 15473 AN: 67960

Other (OTH) AF: 0.216 AC: 452 AN: 2092

Alfa AF: 0.197 Hom.: 405

Bravo AF: 0.188

Asia WGS AF: 0.279 AC: 969 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.14
PhyloP100		-1.7
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: rs7577864; hg19: chr2-70017435;