20-3228242-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001174089.2(SLC4A11):c.2558+17A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,520,830 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0085 (21 hom., cov: 28)
  • Exomes 𝑓: 0.0013 (21 hom.)
• Consequence: SLC4A11 NM_001174089.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.428

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-3228242-T-A is Benign according to our data. Variant chr20-3228242-T-A is described in ClinVar as [Benign]. Clinvar id is 1596059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00847 (1184/139830) while in subpopulation AFR AF= 0.0268 (1007/37570). AF 95% confidence interval is 0.0254. There are 21 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd at 1179 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A11	NM_001174089.2	c.2558+17A>T		intron_variant		ENST00000642402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A11	ENST00000642402.1	c.2558+17A>T		intron_variant			NM_001174089.2	P2

Frequencies

GnomAD3 genomes AF: 0.00844 AC: 1179 AN: 139766 Hom.: 21 Cov.: 28

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00854

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000220

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000115

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.000586

Gnomad OTH AF: 0.00934

GnomAD3 exomes AF: 0.00232 AC: 576 AN: 247882 Hom.: 8 AF XY: 0.00158 AC XY: 213 AN XY: 134700

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.00276

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000566

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00134 AC: 1849 AN: 1381000 Hom.: 21 Cov.: 36 AF XY: 0.00121 AC XY: 831 AN XY: 686322

Gnomad4 AFR exome AF: 0.0300

Gnomad4 AMR exome AF: 0.00334

Gnomad4 ASJ exome AF: 0.0000866

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000935

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000511

Gnomad4 OTH exome AF: 0.00345

GnomAD4 genome AF: 0.00847 AC: 1184 AN: 139830 Hom.: 21 Cov.: 28 AF XY: 0.00783 AC XY: 530 AN XY: 67678

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.00846

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000221

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000115

Gnomad4 NFE AF: 0.000586

Gnomad4 OTH AF: 0.00925

Alfa AF: 0.00351 Hom.: 1

Bravo AF: 0.00941

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.074
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs115581878; hg19: chr20-3208888;