rs6724395

Variant names:

• chr2-69718936-A-G
• rs6724395
• NM_001320698.2:c.-144-1838A>G

Variant summary

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

The NM_001320698.2(ANXA4):​c.-144-1838A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,616 control chromosomes in the GnomAD database, including 6,566 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 0.16 (6566 hom., cov: 32)
• Consequence: ANXA4 NM_001320698.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 6 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]

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 (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA4	NM_001320698.2	c.-144-1838A>G		intron_variant	Intron 2 of 14		NP_001307627.1
ANXA4	XM_017003943.2	c.-144-1838A>G		intron_variant	Intron 3 of 15		XP_016859432.1
ANXA4	XM_024452835.2	c.-144-1838A>G		intron_variant	Intron 3 of 15		XP_024308603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA4	ENST00000418066.2	n.767-1838A>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24804 AN: 151504 Hom.: 6547 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.164 AC: 24869 AN: 151616 Hom.: 6566 Cov.: 32 AF XY: 0.158 AC XY: 11733 AN XY: 74056

African (AFR) AF: 0.556 AC: 22977 AN: 41320

American (AMR) AF: 0.0719 AC: 1094 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3470

East Asian (EAS) AF: 0.00311 AC: 16 AN: 5142

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4806

European-Finnish (FIN) AF: 0.0207 AC: 216 AN: 10422

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 67926

Other (OTH) AF: 0.114 AC: 240 AN: 2102

Alfa AF: 0.0977 Hom.: 463

Bravo AF: 0.186

Asia WGS AF: 0.0500 AC: 174 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6724395; hg19: chr2-69946068;