2-69796337-T-C

Position:

• chr2-69796337-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001153.5(ANXA4):​c.97+8196T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,082 control chromosomes in the GnomAD database, including 7,890 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 0.30 (7890 hom., cov: 31)
• Consequence: ANXA4 NM_001153.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA4	NM_001153.5	c.97+8196T>C		intron_variant		ENST00000394295.6
SMANTIS	NR_164155.1	n.211+2451A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA4	ENST00000394295.6	c.97+8196T>C		intron_variant		1	NM_001153.5	P1
SMANTIS	ENST00000686342.2	n.221+2451A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46149 AN: 151964 Hom.: 7883 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.304 AC: 46186 AN: 152082 Hom.: 7890 Cov.: 31 AF XY: 0.308 AC XY: 22885 AN XY: 74336

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.304

Alfa AF: 0.357 Hom.: 13248

Bravo AF: 0.287

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs7588022; hg19: chr2-70023469;