Variant chr20-3227562-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001174089.2(SLC4A11):c.*225C>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 0.00386 in 592,034 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 28 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 14 hom. )

Consequence

SLC4A11
NM_001174089.2 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.535

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 20-3227562-G-A is Benign according to our data. Variant chr20-3227562-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 338230.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 = 0.0104 (1587/152264) while in subpopulation AFR AF= 0.0362 (1505/41544). AF 95% confidence interval is 0.0347. There are 28 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1587 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A11	NM_001174089.2 linkuse as main transcript	c.*225C>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.*225C>T		3_prime_UTR_variant	20/20		NM_001174089.2	P2	Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1586

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00813

GnomAD4 exome

AF:

0.00159

AC:

698

AN:

439770

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

309

AN XY:

231822

show subpopulations

Gnomad4 AFR exome

AF:

0.0397

Gnomad4 AMR exome

AF:

0.00198

Gnomad4 ASJ exome

AF:

0.00139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000213

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000246

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.0104

AC:

1587

AN:

152264

Hom.:

Cov.:

AF XY:

0.00978

AC XY:

728

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0362

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00598

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Corneal dystrophy

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.7

DANN

Benign

0.67

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