rs12243497

Variant names:

• chr10-73400720-A-T
• rs12243497
• NM_001156.5:c.54+83T>A

Variant summary

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

The NM_001156.5(ANXA7):​c.54+83T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,132,272 control chromosomes in the GnomAD database, including 8,937 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 0.15 (2828 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6109 hom.)
• Consequence: ANXA7 NM_001156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

Genes affected

ANXA7 (HGNC:545): (annexin A7) Annexin VII is a member of the annexin family of calcium-dependent phospholipid binding proteins.The Annexin VII gene contains 14 exons and spans approximately 34 kb of DNA. An alternatively spliced cassette exon results in two mRNA transcripts of 2.0 and 2.4 kb which are predicted to generate two protein isoforms differing in their N-terminal domain. The alternative splicing event is tissue specific and the mRNA containing the cassette exon is prevalent in brain, heart and skeletal muscle. The transcripts also differ in their 3'-non coding regions by the use of two alternative poly(A) signals. Annexin VII encodes a protein with a molecular weight of approximately 51 kDa with a unique, highly hydrophobic N-terminal domain of 167 amino acids and a conserved C-terminal region of 299 amino acids. The latter domain is composed of alternating hydrophobic and hydrophilic segments. Structural analysis of the protein suggests that Annexin VII is a membrane binding protein with diverse properties, including voltage-sensitive calcium channel activity, ion selectivity and membrane fusion. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA7	NM_001156.5	c.54+83T>A		intron_variant	Intron 2 of 12	ENST00000372921.10	NP_001147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA7	ENST00000372921.10	c.54+83T>A		intron_variant	Intron 2 of 12	1	NM_001156.5	ENSP00000362012.4
ANXA7	ENST00000372919.8	c.54+83T>A		intron_variant	Intron 2 of 13	1		ENSP00000362010.4
ANXA7	ENST00000394847.3	c.54+83T>A		intron_variant	Intron 2 of 4	5		ENSP00000378317.3
ANXA7	ENST00000492380.1	n.66-2335T>A		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22901 AN: 152034 Hom.: 2801 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.0883 AC: 86505 AN: 980118 Hom.: 6109 AF XY: 0.0916 AC XY: 45147 AN XY: 493008

Gnomad4 AFR exome AF: 0.323 AC: 6819 AN: 21088

Gnomad4 AMR exome AF: 0.0942 AC: 2478 AN: 26304

Gnomad4 ASJ exome AF: 0.112 AC: 1954 AN: 17372

Gnomad4 EAS exome AF: 0.284 AC: 9276 AN: 32672

Gnomad4 SAS exome AF: 0.218 AC: 12498 AN: 57406

Gnomad4 FIN exome AF: 0.0484 AC: 2324 AN: 48056

Gnomad4 NFE exome AF: 0.0634 AC: 46311 AN: 730564

Gnomad4 Remaining exome AF: 0.106 AC: 4466 AN: 42192

GnomAD4 genome AF: 0.151 AC: 22978 AN: 152154 Hom.: 2828 Cov.: 32 AF XY: 0.152 AC XY: 11297 AN XY: 74410

Gnomad4 AFR AF: 0.317 AC: 0.317118 AN: 0.317118

Gnomad4 AMR AF: 0.101 AC: 0.101099 AN: 0.101099

Gnomad4 ASJ AF: 0.114 AC: 0.113964 AN: 0.113964

Gnomad4 EAS AF: 0.299 AC: 0.298724 AN: 0.298724

Gnomad4 SAS AF: 0.225 AC: 0.225218 AN: 0.225218

Gnomad4 FIN AF: 0.0448 AC: 0.0447958 AN: 0.0447958

Gnomad4 NFE AF: 0.0647 AC: 0.0646988 AN: 0.0646988

Gnomad4 OTH AF: 0.122 AC: 0.122044 AN: 0.122044

Alfa AF: 0.115 Hom.: 234

Bravo AF: 0.160

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Publications

LitVar

Other links and lift over

dbSNP: rs12243497; hg19: chr10-75160478; COSMIC: COSV65824181;