5-151103696-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001155.5(ANXA6):c.1840-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00856 in 1,607,078 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (81 hom.)
• Consequence: ANXA6 NM_001155.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.5999
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.919

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 5-151103696-G-C is Benign according to our data. Variant chr5-151103696-G-C is described in ClinVar as [Benign]. Clinvar id is 717326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA6	NM_001155.5	c.1840-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000354546.10
ANXA6	NM_001193544.2	c.1744-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ANXA6	NM_001363114.2	c.1822-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA6	ENST00000354546.10	c.1840-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001155.5	P4

Frequencies

GnomAD3 genomes AF: 0.00585 AC: 891 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00899

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00709 AC: 1686 AN: 237926 Hom.: 8 AF XY: 0.00759 AC XY: 978 AN XY: 128912

Gnomad AFR exome AF: 0.00151

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0122

Gnomad FIN exome AF: 0.00352

Gnomad NFE exome AF: 0.00962

Gnomad OTH exome AF: 0.00711

GnomAD4 exome AF: 0.00885 AC: 12870 AN: 1454736 Hom.: 81 Cov.: 31 AF XY: 0.00887 AC XY: 6411 AN XY: 723164

Gnomad4 AFR exome AF: 0.00138

Gnomad4 AMR exome AF: 0.00311

Gnomad4 ASJ exome AF: 0.00556

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.00411

Gnomad4 NFE exome AF: 0.00967

Gnomad4 OTH exome AF: 0.00750

GnomAD4 genome AF: 0.00585 AC: 891 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.00563 AC XY: 419 AN XY: 74486

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0125

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.00900

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00671 Hom.: 3

Bravo AF: 0.00578

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	22
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.60
dbscSNV1_RF	Benign	0.50
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.99		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41290563; hg19: chr5-150483257;