Variant chr20-3227753-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001174089.2(SLC4A11):c.*34C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,608,942 control chromosomes in the GnomAD database, including 1,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.065 ( 1026 hom., cov: 33)

Exomes 𝑓: 0.011 ( 968 hom. )

Consequence

SLC4A11
NM_001174089.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.500

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]

SLC4A11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 20-3227753-G-A is Benign according to our data. Variant chr20-3227753-G-A is described in ClinVar as [Benign]. Clinvar id is 338231.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A11	NM_001174089.2 linkuse as main transcript	c.*34C>T		3_prime_UTR_variant	20/20	ENST00000642402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A11	ENST00000642402.1 linkuse as main transcript	c.*34C>T		3_prime_UTR_variant	20/20		NM_001174089.2	P2	Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9880

AN:

152138

Hom.:

1014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0227

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00454

Gnomad OTH

AF:

0.0584

GnomAD3 exomes

AF:

0.0217

AC:

5337

AN:

246020

Hom.:

442

AF XY:

0.0184

AC XY:

2454

AN XY:

133468

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0148

Gnomad ASJ exome

AF:

0.00801

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0218

Gnomad FIN exome

AF:

0.000266

Gnomad NFE exome

AF:

0.00417

Gnomad OTH exome

AF:

0.0144

GnomAD4 exome

AF:

0.0105

AC:

15324

AN:

1456686

Hom.:

968

Cov.:

AF XY:

0.0101

AC XY:

7347

AN XY:

724756

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.00731

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0231

Gnomad4 FIN exome

AF:

0.000216

Gnomad4 NFE exome

AF:

0.00336

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0652

AC:

9920

AN:

152256

Hom.:

1026

Cov.:

AF XY:

0.0628

AC XY:

4674

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.0303

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00454

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0318

Hom.:

181

Bravo

AF:

0.0737

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.27

DANN

Benign

0.45

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

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