5-151137464-C-G

Position:

• chr5-151137464-C-G

Variant summary

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

The NM_001155.5(ANXA6):​c.319-143G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 541,344 control chromosomes in the GnomAD database, including 141,401 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 0.73 (40405 hom., cov: 30)
  • Exomes 𝑓: 0.71 (100996 hom.)
• Consequence: ANXA6 NM_001155.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

Genes affected

ANXA6 (HGNC:544): (annexin A6) Annexin VI belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. The annexin VI gene is approximately 60 kbp long and contains 26 exons. It encodes a protein of about 68 kDa that consists of eight 68-amino acid repeats separated by linking sequences of variable lengths. It is highly similar to human annexins I and II sequences, each of which contain four such repeats. Annexin VI has been implicated in mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA6	NM_001155.5	c.319-143G>C		intron_variant		ENST00000354546.10
ANXA6	NM_001193544.2	c.223-143G>C		intron_variant
ANXA6	NM_001363114.2	c.319-143G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA6	ENST00000354546.10	c.319-143G>C		intron_variant		1	NM_001155.5	P4

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110345 AN: 151894 Hom.: 40352 Cov.: 30

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.708

GnomAD4 exome AF: 0.714 AC: 277969 AN: 389332 Hom.: 100996 AF XY: 0.720 AC XY: 147397 AN XY: 204786

Gnomad4 AFR exome AF: 0.770

Gnomad4 AMR exome AF: 0.758

Gnomad4 ASJ exome AF: 0.601

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.863

Gnomad4 FIN exome AF: 0.686

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.727 AC: 110454 AN: 152012 Hom.: 40405 Cov.: 30 AF XY: 0.730 AC XY: 54215 AN XY: 74290

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.711

Alfa AF: 0.687 Hom.: 4498

Bravo AF: 0.731

Asia WGS AF: 0.862 AC: 2999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9324679; hg19: chr5-150517025; COSMIC: COSV62906014; COSMIC: COSV62906014;