rs41281862

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174089.2(SLC4A11):​c.1283-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,268 control chromosomes in the GnomAD database, including 12,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 879 hom., cov: 34)
Exomes 𝑓: 0.12 ( 11404 hom. )

Consequence

SLC4A11
NM_001174089.2 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0001945
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.43
Variant links:
Genes affected
SLC4A11 (HGNC:16438): (solute carrier family 4 member 11) This gene encodes a voltage-regulated, electrogenic sodium-coupled borate cotransporter that is essential for borate homeostasis, cell growth and cell proliferation. Mutations in this gene have been associated with a number of endothelial corneal dystrophies including recessive corneal endothelial dystrophy 2, corneal dystrophy and perceptive deafness, and Fuchs endothelial corneal dystrophy. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

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=-0.73).
BP6
Variant 20-3230658-G-A is Benign according to our data. Variant chr20-3230658-G-A is described in ClinVar as [Benign]. Clinvar id is 261994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC4A11NM_001174089.2 linkuse as main transcriptc.1283-11C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000642402.1 NP_001167560.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC4A11ENST00000642402.1 linkuse as main transcriptc.1283-11C>T splice_polypyrimidine_tract_variant, intron_variant NM_001174089.2 ENSP00000493503 P2Q8NBS3-3

Frequencies

GnomAD3 genomes
AF:
0.0945
AC:
14377
AN:
152172
Hom.:
880
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0381
Gnomad AMI
AF:
0.0989
Gnomad AMR
AF:
0.0945
Gnomad ASJ
AF:
0.130
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.0300
Gnomad FIN
AF:
0.130
Gnomad MID
AF:
0.0924
Gnomad NFE
AF:
0.133
Gnomad OTH
AF:
0.106
GnomAD3 exomes
AF:
0.0975
AC:
24397
AN:
250252
Hom.:
1479
AF XY:
0.0975
AC XY:
13206
AN XY:
135432
show subpopulations
Gnomad AFR exome
AF:
0.0352
Gnomad AMR exome
AF:
0.0768
Gnomad ASJ exome
AF:
0.139
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0306
Gnomad FIN exome
AF:
0.133
Gnomad NFE exome
AF:
0.135
Gnomad OTH exome
AF:
0.117
GnomAD4 exome
AF:
0.118
AC:
173096
AN:
1460978
Hom.:
11404
Cov.:
57
AF XY:
0.116
AC XY:
84612
AN XY:
726788
show subpopulations
Gnomad4 AFR exome
AF:
0.0339
Gnomad4 AMR exome
AF:
0.0807
Gnomad4 ASJ exome
AF:
0.141
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0312
Gnomad4 FIN exome
AF:
0.131
Gnomad4 NFE exome
AF:
0.133
Gnomad4 OTH exome
AF:
0.108
GnomAD4 genome
AF:
0.0944
AC:
14376
AN:
152290
Hom.:
879
Cov.:
34
AF XY:
0.0927
AC XY:
6899
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0381
Gnomad4 AMR
AF:
0.0944
Gnomad4 ASJ
AF:
0.130
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.0304
Gnomad4 FIN
AF:
0.130
Gnomad4 NFE
AF:
0.133
Gnomad4 OTH
AF:
0.105
Alfa
AF:
0.109
Hom.:
294
Bravo
AF:
0.0887
Asia WGS
AF:
0.0190
AC:
67
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Corneal dystrophy Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Corneal dystrophy-perceptive deafness syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -
Congenital hereditary endothelial dystrophy of cornea Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.059
DANN
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00019
dbscSNV1_RF
Benign
0.016
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

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

Other links and lift over

dbSNP: rs41281862; hg19: chr20-3211304; API