rs3803953

Variant names:

• chr20-3231073-T-G
• rs3803953
• NM_001174089.2:c.1043-15A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-3231073-T-G
• chr20-3231073-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001174089.2(SLC4A11):​c.1043-15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,606,584 control chromosomes in the GnomAD database, including 165,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (13606 hom., cov: 32)
  • Exomes 𝑓: 0.45 (151812 hom.)
• Consequence: SLC4A11 NM_001174089.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.16
• Publications: 12 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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• congenital hereditary endothelial dystrophy of cornea

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-3231073-T-G is Benign according to our data. Variant chr20-3231073-T-G is described in ClinVar as Benign. ClinVar VariationId is 261993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	NM_001174089.2	MANE Select	c.1043-15A>C		intron	N/A	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.1172-15A>C		intron	N/A	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.1091-15A>C		intron	N/A	NP_114423.1	Q8NBS3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	ENST00000642402.1	MANE Select	c.1043-15A>C		intron	N/A	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.1091-15A>C		intron	N/A	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000380059.7	TSL:2	c.1172-15A>C		intron	N/A	ENSP00000369399.3	Q8NBS3-4

Frequencies

GnomAD3 genomes AF: 0.435 AC: 63278 AN: 145596 Hom.: 13591 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.438

GnomAD2 exomes AF: 0.453 AC: 112844 AN: 248962 AF XY: 0.449

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.535

Gnomad ASJ exome AF: 0.507

Gnomad EAS exome AF: 0.483

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.454 AC: 662808 AN: 1460902 Hom.: 151812 Cov.: 77 AF XY: 0.452 AC XY: 328160 AN XY: 726790

African (AFR) AF: 0.304 AC: 9944 AN: 32734

American (AMR) AF: 0.525 AC: 23471 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 13283 AN: 26136

East Asian (EAS) AF: 0.445 AC: 17673 AN: 39694

South Asian (SAS) AF: 0.374 AC: 32239 AN: 86244

European-Finnish (FIN) AF: 0.433 AC: 23090 AN: 53356

Middle Eastern (MID) AF: 0.508 AC: 2925 AN: 5762

European-Non Finnish (NFE) AF: 0.462 AC: 513201 AN: 1111984

Other (OTH) AF: 0.447 AC: 26982 AN: 60312

GnomAD4 genome AF: 0.435 AC: 63334 AN: 145682 Hom.: 13606 Cov.: 32 AF XY: 0.433 AC XY: 30912 AN XY: 71320

African (AFR) AF: 0.359 AC: 12665 AN: 35258

American (AMR) AF: 0.489 AC: 7431 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2496 AN: 5162

South Asian (SAS) AF: 0.355 AC: 1711 AN: 4820

European-Finnish (FIN) AF: 0.442 AC: 4676 AN: 10568

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31023 AN: 67934

Other (OTH) AF: 0.439 AC: 911 AN: 2076

Alfa AF: 0.343 Hom.: 3088

Bravo AF: 0.421

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Congenital hereditary endothelial dystrophy of cornea (1)
-	-	1	Corneal dystrophy (1)
-	-	1	Corneal dystrophy-perceptive deafness syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.013
DANN	Benign	0.47
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3803953; hg19: chr20-3211719; COSMIC: COSV66261636; COSMIC: COSV66261636;