chr20-3229655-G-A

Variant names:

• chr20-3229655-G-A
• rs41281860
• NM_001174089.2:c.1611C>T
• SLC4A11 p.Asn537Asn

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001174089.2(SLC4A11):​c.1611C>T​(p.Asn537Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,742 control chromosomes in the GnomAD database, including 11,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (806 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10278 hom.)
• Consequence: SLC4A11 NM_001174089.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0100
• 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, 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 20-3229655-G-A is Benign according to our data. Variant chr20-3229655-G-A is described in ClinVar as Benign. ClinVar VariationId is 261997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 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.1611C>T	p.Asn537Asn	synonymous	Exon 14 of 20	NP_001167560.1	Q8NBS3-3
	SLC4A11	NM_001174090.2		c.1740C>T	p.Asn580Asn	synonymous	Exon 14 of 20	NP_001167561.1	Q8NBS3-4
	SLC4A11	NM_032034.4		c.1659C>T	p.Asn553Asn	synonymous	Exon 13 of 19	NP_114423.1	Q8NBS3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	ENST00000642402.1	MANE Select	c.1611C>T	p.Asn537Asn	synonymous	Exon 14 of 20	ENSP00000493503.1	Q8NBS3-3
	SLC4A11	ENST00000380056.7	TSL:1	c.1659C>T	p.Asn553Asn	synonymous	Exon 13 of 19	ENSP00000369396.3	Q8NBS3-1
	SLC4A11	ENST00000876659.1		c.1541C>T	p.Thr514Met	missense	Exon 14 of 20	ENSP00000546718.1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13783 AN: 152180 Hom.: 807 Cov.: 33

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0285

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0976

GnomAD2 exomes AF: 0.0935 AC: 23433 AN: 250636 AF XY: 0.0935

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.0707

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.00245

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.113 AC: 164700 AN: 1461444 Hom.: 10278 Cov.: 46 AF XY: 0.111 AC XY: 80547 AN XY: 727046

African (AFR) AF: 0.0305 AC: 1021 AN: 33476

American (AMR) AF: 0.0744 AC: 3327 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3540 AN: 26130

East Asian (EAS) AF: 0.00464 AC: 184 AN: 39696

South Asian (SAS) AF: 0.0291 AC: 2511 AN: 86250

European-Finnish (FIN) AF: 0.142 AC: 7534 AN: 53102

Middle Eastern (MID) AF: 0.0733 AC: 421 AN: 5742

European-Non Finnish (NFE) AF: 0.126 AC: 139891 AN: 1111960

Other (OTH) AF: 0.104 AC: 6271 AN: 60376

GnomAD4 genome AF: 0.0905 AC: 13782 AN: 152298 Hom.: 806 Cov.: 33 AF XY: 0.0898 AC XY: 6688 AN XY: 74468

African (AFR) AF: 0.0343 AC: 1428 AN: 41578

American (AMR) AF: 0.0910 AC: 1393 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3468

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5178

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4832

European-Finnish (FIN) AF: 0.141 AC: 1501 AN: 10618

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.126 AC: 8545 AN: 68004

Other (OTH) AF: 0.0971 AC: 205 AN: 2112

Alfa AF: 0.110 Hom.: 525

Bravo AF: 0.0837

Asia WGS AF: 0.0180 AC: 62 AN: 3478

EpiCase AF: 0.128

EpiControl AF: 0.127

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Corneal dystrophy-perceptive deafness syndrome (2)
-	-	2	not provided (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	0.14
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		0.010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs41281860;

hg19: chr20-3210301;

COSMIC: COSV66260334;

COSMIC: COSV66260334;