5-151105226-C-T

Position:

• chr5-151105226-C-T

Variant summary

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

The NM_001155.5(ANXA6):​c.1839+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 1,610,606 control chromosomes in the GnomAD database, including 7,907 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 0.12 (2209 hom., cov: 33)
  • Exomes 𝑓: 0.057 (5698 hom.)
• Consequence: ANXA6 NM_001155.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA6	NM_001155.5	c.1839+19G>A		intron_variant		ENST00000354546.10	NP_001146.2
ANXA6	NM_001193544.2	c.1743+19G>A		intron_variant			NP_001180473.1
ANXA6	NM_001363114.2	c.1821+19G>A		intron_variant			NP_001350043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10	c.1839+19G>A		intron_variant		1	NM_001155.5	ENSP00000346550	P4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18744 AN: 152086 Hom.: 2202 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.0929

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.0862 AC: 21483 AN: 249164 Hom.: 1983 AF XY: 0.0888 AC XY: 12004 AN XY: 135178

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.0441

Gnomad ASJ exome AF: 0.0915

Gnomad EAS exome AF: 0.140

Gnomad SAS exome AF: 0.221

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.0362

Gnomad OTH exome AF: 0.0730

GnomAD4 exome AF: 0.0567 AC: 82681 AN: 1458402 Hom.: 5698 Cov.: 30 AF XY: 0.0609 AC XY: 44184 AN XY: 725672

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.0485

Gnomad4 ASJ exome AF: 0.0898

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.0209

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.0774

GnomAD4 genome AF: 0.123 AC: 18780 AN: 152204 Hom.: 2209 Cov.: 33 AF XY: 0.124 AC XY: 9205 AN XY: 74434

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.0929

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0177

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0559 Hom.: 204

Bravo AF: 0.133

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.65

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: rs884520; hg19: chr5-150484787; COSMIC: COSV62905542;