rs3803957

Variant names:

• chr20-3234902-C-A
• rs3803957
• NM_001174089.2:c.89-8G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3234902-C-A
• chr20-3234902-C-G
• chr20-3234902-C-T

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.89-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,613,366 control chromosomes in the GnomAD database, including 67,813 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6151 hom., cov: 32)
  • Exomes 𝑓: 0.29 (61662 hom.)
• Consequence: SLC4A11 NM_001174089.2 splice_region, intron
• Scores: Splicing: ADA: 0.0001658
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.903
• Publications: 8 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=-0.61).
• BP6: Variant 20-3234902-C-A is Benign according to our data. Variant chr20-3234902-C-A is described in ClinVar as Benign. ClinVar VariationId is 261995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 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.89-8G>T		splice_region intron	N/A	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.218-8G>T		splice_region intron	N/A	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.137-8G>T		splice_region 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.89-8G>T		splice_region intron	N/A	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.137-8G>T		splice_region intron	N/A	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000380059.7	TSL:2	c.218-8G>T		splice_region intron	N/A	ENSP00000369399.3	Q8NBS3-4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42499 AN: 151936 Hom.: 6148 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.306 AC: 76467 AN: 249978 AF XY: 0.302

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.402

Gnomad FIN exome AF: 0.381

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.287 AC: 419874 AN: 1461314 Hom.: 61662 Cov.: 41 AF XY: 0.287 AC XY: 208652 AN XY: 726912

African (AFR) AF: 0.202 AC: 6762 AN: 33476

American (AMR) AF: 0.368 AC: 16436 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 7320 AN: 26132

East Asian (EAS) AF: 0.373 AC: 14807 AN: 39700

South Asian (SAS) AF: 0.258 AC: 22215 AN: 86250

European-Finnish (FIN) AF: 0.376 AC: 19955 AN: 53088

Middle Eastern (MID) AF: 0.280 AC: 1614 AN: 5768

European-Non Finnish (NFE) AF: 0.282 AC: 313402 AN: 1111806

Other (OTH) AF: 0.288 AC: 17363 AN: 60386

GnomAD4 genome AF: 0.280 AC: 42513 AN: 152052 Hom.: 6151 Cov.: 32 AF XY: 0.287 AC XY: 21312 AN XY: 74298

African (AFR) AF: 0.211 AC: 8770 AN: 41476

American (AMR) AF: 0.347 AC: 5303 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2072 AN: 5150

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4816

European-Finnish (FIN) AF: 0.396 AC: 4185 AN: 10574

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19032 AN: 67970

Other (OTH) AF: 0.268 AC: 564 AN: 2106

Alfa AF: 0.279 Hom.: 4099

Bravo AF: 0.274

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Corneal dystrophy-perceptive deafness syndrome (2)
-	-	2	not specified (2)
-	-	1	Congenital hereditary endothelial dystrophy of cornea (1)
-	-	1	Corneal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.3
DANN	Benign	0.81
PhyloP100		-0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.030
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: rs3803957; hg19: chr20-3215548; COSMIC: COSV66262164; COSMIC: COSV66262164;