rs6051669

Variant names:

• chr20-3235557-T-C
• rs6051669
• NM_001174089.2:c.89-663A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• corneal dystrophy, Fuchs endothelial, 4

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• congenital hereditary endothelial dystrophy of cornea

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• corneal dystrophy-perceptive deafness syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• Fuchs' endothelial dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174089.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	NM_001174089.2	MANE Select	c.89-663A>G		intron	N/A	NP_001167560.1
	SLC4A11	NM_001174090.2		c.218-663A>G		intron	N/A	NP_001167561.1
	SLC4A11	NM_032034.4		c.137-663A>G		intron	N/A	NP_114423.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	ENST00000642402.1	MANE Select	c.89-663A>G		intron	N/A	ENSP00000493503.1
	SLC4A11	ENST00000380056.7	TSL:1	c.137-663A>G		intron	N/A	ENSP00000369396.3
	SLC4A11	ENST00000380059.7	TSL:2	c.218-663A>G		intron	N/A	ENSP00000369399.3

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

African (AFR) AF: 0.779 AC: 32236 AN: 41386

American (AMR) AF: 0.635 AC: 9705 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1932 AN: 3472

East Asian (EAS) AF: 0.711 AC: 3659 AN: 5148

South Asian (SAS) AF: 0.519 AC: 2502 AN: 4818

European-Finnish (FIN) AF: 0.613 AC: 6480 AN: 10566

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39762 AN: 67870

Other (OTH) AF: 0.617 AC: 1300 AN: 2108

Alfa AF: 0.570 Hom.: 9221

Bravo AF: 0.656

Asia WGS AF: 0.558 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.77
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6051669; hg19: chr20-3216203;