Variant 5-151103696-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Variant links:

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]

ANXA6 links:

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ACMG classification

Classification made for transcript

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 GnomAdExome4 at 81 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ANXA6	NM_001155.5 linkuse as main transcript	c.1840-4C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000354546.10	NP_001146.2
ANXA6	NM_001193544.2 linkuse as main transcript	c.1744-4C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001180473.1
ANXA6	NM_001363114.2 linkuse as main transcript	c.1822-4C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001350043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA6	ENST00000354546.10 linkuse as main transcript	c.1840-4C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001155.5	ENSP00000346550	P4	P08133-1

Frequencies

GnomAD3 genomes

AF:

0.00585

AC:

891

AN:

152224

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00759

AC XY:

978

AN XY:

128912

show subpopulations

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.:

Cov.:

AF XY:

0.00887

AC XY:

6411

AN XY:

723164

show subpopulations

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.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74486

show subpopulations

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.:

Bravo

AF:

0.00578

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over