chr10-80157637-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145868.2(ANXA11):​c.1458+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000945 in 1,612,450 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00052 ( 3 hom. )

Consequence

ANXA11
NM_145868.2 splice_donor_region, intron

Scores

2
Splicing: ADA: 0.00006004
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.954
Variant links:
Genes affected
ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 10-80157637-G-A is Benign according to our data. Variant chr10-80157637-G-A is described in ClinVar as [Benign]. Clinvar id is 1643018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00501 (763/152174) while in subpopulation AFR AF= 0.017 (706/41534). AF 95% confidence interval is 0.016. There are 4 homozygotes in gnomad4. There are 338 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 763 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANXA11NM_145868.2 linkuse as main transcriptc.1458+4C>T splice_donor_region_variant, intron_variant ENST00000422982.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANXA11ENST00000422982.8 linkuse as main transcriptc.1458+4C>T splice_donor_region_variant, intron_variant 1 NM_145868.2 P2P50995-1

Frequencies

GnomAD3 genomes
AF:
0.00498
AC:
757
AN:
152056
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00127
AC:
317
AN:
249934
Hom.:
1
AF XY:
0.000970
AC XY:
131
AN XY:
135100
show subpopulations
Gnomad AFR exome
AF:
0.0153
Gnomad AMR exome
AF:
0.00119
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000427
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000798
Gnomad OTH exome
AF:
0.000822
GnomAD4 exome
AF:
0.000521
AC:
761
AN:
1460276
Hom.:
3
Cov.:
32
AF XY:
0.000441
AC XY:
320
AN XY:
726296
show subpopulations
Gnomad4 AFR exome
AF:
0.0144
Gnomad4 AMR exome
AF:
0.00130
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000325
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000109
Gnomad4 OTH exome
AF:
0.000994
GnomAD4 genome
AF:
0.00501
AC:
763
AN:
152174
Hom.:
4
Cov.:
32
AF XY:
0.00454
AC XY:
338
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0170
Gnomad4 AMR
AF:
0.00203
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00228
Hom.:
1
Bravo
AF:
0.00562
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.0000593

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 submitterclinical testingInvitaeDec 04, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.0030
DANN
Benign
0.54
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000060
dbscSNV1_RF
Benign
0.11
SpliceAI score (max)
0.050
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

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

Other links and lift over

dbSNP: rs79950900; hg19: chr10-81917393; API