rs12258241

Positions:

• chr10-73400499-C-A
• chr10-73400499-C-T

Variant summary

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

The ENST00000372921.10(ANXA7):​c.54+304G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,024 control chromosomes in the GnomAD database, including 4,980 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 0.19 (4980 hom., cov: 32)
• Consequence: ANXA7 ENST00000372921.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA7	NM_001156.5	c.54+304G>T		intron_variant		ENST00000372921.10	NP_001147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA7	ENST00000372921.10	c.54+304G>T		intron_variant		1	NM_001156.5	ENSP00000362012	P2
ANXA7	ENST00000372919.8	c.54+304G>T		intron_variant		1		ENSP00000362010	A2
ANXA7	ENST00000394847.3	c.54+304G>T		intron_variant		5		ENSP00000378317
ANXA7	ENST00000492380.1	n.66-2114G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28659 AN: 151906 Hom.: 4954 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.189 AC: 28740 AN: 152024 Hom.: 4980 Cov.: 32 AF XY: 0.189 AC XY: 14031 AN XY: 74292

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.146

Alfa AF: 0.0750 Hom.: 656

Bravo AF: 0.203

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.47

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: rs12258241; hg19: chr10-75160257;