20-3233374-G-T

Variant names:

• chr20-3233374-G-T
• rs2144771
• NM_001174089.2:c.729+140C>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.729+140C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,248,768 control chromosomes in the GnomAD database, including 172,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20269 hom., cov: 32)
  • Exomes 𝑓: 0.52 (151836 hom.)
• Consequence: SLC4A11 NM_001174089.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.154
• Publications: 3 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), G2P
• congenital hereditary endothelial dystrophy of cornea

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

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• 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=-0.89).
• BP6: Variant 20-3233374-G-T is Benign according to our data. Variant chr20-3233374-G-T is described in ClinVar as [Benign]. Clinvar id is 1184767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.729+140C>A		intron_variant	Intron 7 of 19	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.729+140C>A		intron_variant	Intron 7 of 19		NM_001174089.2	ENSP00000493503.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77870 AN: 151686 Hom.: 20241 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.524 AC: 574553 AN: 1096964 Hom.: 151836 AF XY: 0.525 AC XY: 290075 AN XY: 552224

African (AFR) AF: 0.521 AC: 13871 AN: 26614

American (AMR) AF: 0.531 AC: 19528 AN: 36768

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 11074 AN: 21378

East Asian (EAS) AF: 0.535 AC: 19253 AN: 35972

South Asian (SAS) AF: 0.609 AC: 43741 AN: 71806

European-Finnish (FIN) AF: 0.405 AC: 14146 AN: 34932

Middle Eastern (MID) AF: 0.511 AC: 2469 AN: 4834

European-Non Finnish (NFE) AF: 0.521 AC: 425282 AN: 816738

Other (OTH) AF: 0.526 AC: 25189 AN: 47922

GnomAD4 genome AF: 0.513 AC: 77947 AN: 151804 Hom.: 20269 Cov.: 32 AF XY: 0.507 AC XY: 37646 AN XY: 74184

African (AFR) AF: 0.517 AC: 21394 AN: 41386

American (AMR) AF: 0.523 AC: 7978 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3470

East Asian (EAS) AF: 0.523 AC: 2678 AN: 5124

South Asian (SAS) AF: 0.611 AC: 2941 AN: 4812

European-Finnish (FIN) AF: 0.365 AC: 3845 AN: 10538

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35547 AN: 67910

Other (OTH) AF: 0.548 AC: 1156 AN: 2108

Alfa AF: 0.521 Hom.: 7376

Bravo AF: 0.522

Asia WGS AF: 0.623 AC: 2164 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Corneal dystrophy-perceptive deafness syndrome Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital hereditary endothelial dystrophy of cornea Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.77
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2144771; hg19: chr20-3214020;