rs41281862

Variant names:

• chr20-3230658-G-A
• rs41281862
• NM_001174089.2:c.1283-11C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3230658-G-A
• chr20-3230658-G-C
• chr20-3230658-G-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.1283-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,268 control chromosomes in the GnomAD database, including 12,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (879 hom., cov: 34)
  • Exomes 𝑓: 0.12 (11404 hom.)
• Consequence: SLC4A11 NM_001174089.2 intron
• Scores: Splicing: ADA: 0.0001945
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.43
• 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), PanelApp Australia, G2P
• congenital hereditary endothelial dystrophy of cornea

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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=-0.73).
• BP6: Variant 20-3230658-G-A is Benign according to our data. Variant chr20-3230658-G-A is described in ClinVar as Benign. ClinVar VariationId is 261994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 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.1283-11C>T		intron	N/A	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.1412-11C>T		intron	N/A	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.1331-11C>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.1283-11C>T		intron	N/A	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.1331-11C>T		intron	N/A	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000380059.7	TSL:2	c.1412-11C>T		intron	N/A	ENSP00000369399.3	Q8NBS3-4

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14377 AN: 152172 Hom.: 880 Cov.: 34

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.0975 AC: 24397 AN: 250252 AF XY: 0.0975

Gnomad AFR exome AF: 0.0352

Gnomad AMR exome AF: 0.0768

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.118 AC: 173096 AN: 1460978 Hom.: 11404 Cov.: 57 AF XY: 0.116 AC XY: 84612 AN XY: 726788

African (AFR) AF: 0.0339 AC: 1135 AN: 33480

American (AMR) AF: 0.0807 AC: 3608 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 3691 AN: 26136

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39700

South Asian (SAS) AF: 0.0312 AC: 2689 AN: 86258

European-Finnish (FIN) AF: 0.131 AC: 6882 AN: 52534

Middle Eastern (MID) AF: 0.0759 AC: 438 AN: 5768

European-Non Finnish (NFE) AF: 0.133 AC: 148132 AN: 1111994

Other (OTH) AF: 0.108 AC: 6513 AN: 60386

GnomAD4 genome AF: 0.0944 AC: 14376 AN: 152290 Hom.: 879 Cov.: 34 AF XY: 0.0927 AC XY: 6899 AN XY: 74462

African (AFR) AF: 0.0381 AC: 1582 AN: 41572

American (AMR) AF: 0.0944 AC: 1444 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0304 AC: 147 AN: 4828

European-Finnish (FIN) AF: 0.130 AC: 1378 AN: 10624

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9033 AN: 67986

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.107 Hom.: 460

Bravo AF: 0.0887

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	-0.73
CADD	Benign	0.059
DANN	Benign	0.81
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.016
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: rs41281862;

hg19: chr20-3211304;

COSMIC: COSV107496169;

COSMIC: COSV107496169;