rs6051669

Positions:

• chr20-3235557-T-C
• chr20-3235557-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174089.2(SLC4A11):​c.89-663A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,848 control chromosomes in the GnomAD database, including 32,412 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32412 hom., cov: 30)
• Consequence: SLC4A11 NM_001174089.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.89-663A>G		intron_variant		ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.89-663A>G		intron_variant			NM_001174089.2	ENSP00000493503	P2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98198 AN: 151730 Hom.: 32383 Cov.: 30

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.620

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.647 AC: 98272 AN: 151848 Hom.: 32412 Cov.: 30 AF XY: 0.647 AC XY: 48007 AN XY: 74238

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.617

Alfa AF: 0.542 Hom.: 3917

Bravo AF: 0.656

Asia WGS AF: 0.558 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs6051669; hg19: chr20-3216203;