rs9324677

Positions:

• chr5-151134177-A-C
• chr5-151134177-A-T

Variant summary

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

The NM_001155.5(ANXA6):​c.546+250T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,150 control chromosomes in the GnomAD database, including 27,602 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 0.60 (27602 hom., cov: 33)
• Consequence: ANXA6 NM_001155.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA6	NM_001155.5	c.546+250T>G		intron_variant		ENST00000354546.10
ANXA6	NM_001193544.2	c.450+250T>G		intron_variant
ANXA6	NM_001363114.2	c.546+250T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA6	ENST00000354546.10	c.546+250T>G		intron_variant		1	NM_001155.5	P4

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90560 AN: 152032 Hom.: 27562 Cov.: 33

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.596 AC: 90645 AN: 152150 Hom.: 27602 Cov.: 33 AF XY: 0.596 AC XY: 44342 AN XY: 74370

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.577

Alfa AF: 0.555 Hom.: 47457

Bravo AF: 0.592

Asia WGS AF: 0.519 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.80
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: rs9324677; hg19: chr5-150513738;