rs41281858

Variant names:

• chr20-3228437-G-A
• rs41281858
• NM_001174089.2:c.2389-9C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3228437-G-A
• chr20-3228437-G-C

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.2389-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,612,928 control chromosomes in the GnomAD database, including 15,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2542 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13247 hom.)
• Consequence: SLC4A11 NM_001174089.2 intron
• Scores: Splicing: ADA: 0.00001559
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.473
• Publications: 10 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet
• corneal dystrophy-perceptive deafness syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.84).
• BP6: Variant 20-3228437-G-A is Benign according to our data. Variant chr20-3228437-G-A is described in ClinVar as Benign. ClinVar VariationId is 261999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 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.2389-9C>T		intron	N/A	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.2518-9C>T		intron	N/A	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.2437-9C>T		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.2389-9C>T		intron	N/A	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.2437-9C>T		intron	N/A	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000380059.7	TSL:2	c.2518-9C>T		intron	N/A	ENSP00000369399.3	Q8NBS3-4

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25604 AN: 152006 Hom.: 2538 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.170

GnomAD2 exomes AF: 0.128 AC: 32070 AN: 250404 AF XY: 0.124

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.0889

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.131

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.130 AC: 189529 AN: 1460804 Hom.: 13247 Cov.: 45 AF XY: 0.127 AC XY: 92415 AN XY: 726724

African (AFR) AF: 0.280 AC: 9364 AN: 33476

American (AMR) AF: 0.0945 AC: 4225 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3502 AN: 26126

East Asian (EAS) AF: 0.136 AC: 5400 AN: 39696

South Asian (SAS) AF: 0.0549 AC: 4731 AN: 86248

European-Finnish (FIN) AF: 0.147 AC: 7709 AN: 52486

Middle Eastern (MID) AF: 0.0967 AC: 558 AN: 5768

European-Non Finnish (NFE) AF: 0.131 AC: 145803 AN: 1111904

Other (OTH) AF: 0.136 AC: 8237 AN: 60380

GnomAD4 genome AF: 0.168 AC: 25626 AN: 152124 Hom.: 2542 Cov.: 31 AF XY: 0.167 AC XY: 12391 AN XY: 74364

African (AFR) AF: 0.274 AC: 11379 AN: 41474

American (AMR) AF: 0.130 AC: 1988 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3472

East Asian (EAS) AF: 0.121 AC: 621 AN: 5146

South Asian (SAS) AF: 0.0646 AC: 312 AN: 4828

European-Finnish (FIN) AF: 0.146 AC: 1547 AN: 10604

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.130 AC: 8811 AN: 67982

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.150 Hom.: 927

Bravo AF: 0.172

Asia WGS AF: 0.111 AC: 386 AN: 3476

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
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.020
DANN	Benign	0.85
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41281858;

hg19: chr20-3209083;

COSMIC: COSV66262259;

COSMIC: COSV66262259;