10-73375688-C-T

Position:

• chr10-73375688-C-T

Variant summary

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

The NM_001156.5(ANXA7):​c.*407G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,966 control chromosomes in the GnomAD database, including 70,339 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 0.96 (69997 hom., cov: 30)
  • Exomes 𝑓: 0.95 (342 hom.)
• Consequence: ANXA7 NM_001156.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA7	NM_001156.5	c.*407G>A		3_prime_UTR_variant	13/13	ENST00000372921.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA7	ENST00000372921.10	c.*407G>A		3_prime_UTR_variant	13/13	1	NM_001156.5	P2
ANXA7	ENST00000372919.8	c.*407G>A		3_prime_UTR_variant	14/14	1		A2
ANXA7	ENST00000463788.1	n.700G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145789 AN: 152100 Hom.: 69937 Cov.: 30

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.947

GnomAD4 exome AF: 0.955 AC: 714 AN: 748 Hom.: 342 Cov.: 0 AF XY: 0.964 AC XY: 401 AN XY: 416

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.941

Gnomad4 OTH exome AF: 0.955

GnomAD4 genome AF: 0.959 AC: 145908 AN: 152218 Hom.: 69997 Cov.: 30 AF XY: 0.960 AC XY: 71411 AN XY: 74418

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.960

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.992

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.947

Alfa AF: 0.942 Hom.: 81916

Bravo AF: 0.962

Asia WGS AF: 0.993 AC: 3443 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.52

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: rs6896; hg19: chr10-75135446;